Influenzavirus A
Encyclopedia
Influenza A virus causes influenza
in bird
s and some mammal
s and is the only species
of Influenzavirus A. Influenzavirus A is a genus
of the Orthomyxoviridae
family of virus
es. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon. Some isolates
of influenza A virus cause severe disease both in domestic poultry and, rarely, in human
s. Occasionally viruses are transmitted from wild aquatic birds to domestic poultry and this may cause an outbreak or give rise to human influenza pandemic
s.
Influenza A viruses are negative sense
, single-stranded, segmented RNA virus
es.
There are several subtypes, labeled according to an H number (for the type of hemagglutinin) and an N number (for the type of neuraminidase
). There are 16 different H antigen
s (H1 to H16) and nine different N antigens (N1 to N9). The newest H type (H16) was isolated from black-headed gull
s caught in Sweden
and the Netherlands
in 1999 and reported in the literature in 2005.
Each virus subtype has mutate
d into a variety of strains with differing pathogen
ic profiles; some pathogenic to one species but not others, some pathogenic to multiple species.
A filtered and purified influenza A vaccine for humans was developed and many countries have stockpiled it to allow a quick administration to the population in the event of an avian influenza pandemic. Avian influenza is sometimes called avian flu, and commonly bird flu. In 2011, researchers reported the discovery of an antibody effective against all types of the influenza A virus.
Different influenza viruses encode for different hemagglutinin and neuraminidase proteins. For example, the H5N1 virus designates an influenza A subtype that has a type 5 hemagglutinin (H) protein and a type 1 neuraminidase (N) protein. There are 16 known types of hemagglutinin and 9 known types of neuraminidase, so, in theory, 144 different combinations of these proteins are possible.
Some variants are identified and named according to the isolate that they are like and thus are presumed to share lineage (example Fujian flu
virus like); according to their typical host (example human flu
virus); according to their subtype (example H3N2); and according to their deadliness (example LP, Low Pathogenic). So a flu from a virus similar to the isolate A/Fujian/411/2002(H3N2) is called Fujian
flu, human flu, and H3N2 flu.
Variants are sometimes named according to the species (host) the strain is endemic in or adapted to. The main variants named using this convention are:
Variants have also sometimes been named according to their deadliness in poultry, especially chickens:
Most known strains are extinct strains. For example, the annual flu subtype H3N2 no longer contains the strain that caused the Hong Kong flu
.
in the U.S. "results in approximately 36,000 deaths and more than 200,000 hospitalizations each year. In addition to this human toll, influenza is annually responsible for a total cost of over $10 billion in the U.S.".
The annually updated trivalent influenza vaccine consists of hemagglutinin
(HA) surface glycoprotein components from influenza H3N2, H1N1, and B influenza
viruses.
Measured resistance to the standard antiviral drugs amantadine
and rimantadine
in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005.
"[C]ontemporary human H3N2 influenza viruses are now endemic
in pig
s in southern China
and can reassort
with avian H5N1 viruses in this intermediate host." "H5N1 virus is now endemic in poultry in Asia (Table 2-1) and has gained an entrenched ecological niche from which to present a long-term pandemic threat to humans. At present, these viruses are poorly transmitted from poultry to humans, and there is no conclusive evidence of human-to-human transmission. However, continued, extensive exposure of the human population to H5N1 viruses increases the likelihood that the viruses will acquire the necessary characteristics for efficient human-to-human transmission through genetic mutation or reassortment with a prevailing human influenza A virus. Furthermore, contemporary human H3N2 influenza viruses are now endemic in pigs in southern China (Peiris et al., 2001) and can reassort with avian H5N1 viruses in this 'intermediate host.' Therefore, it is imperative that outbreaks of H5N1 disease in poultry in Asia are rapidly and sustainably controlled. The seasonality of the disease in poultry, together with the control measures already implemented, are likely to reduce temporarily the frequency of H5N1 influenza outbreaks and the probability of human infection."
that targets the hemagglutinin protein, was recently discovered and is the only known antibody effective against all 16 subtypes of the influenza A virus.
The Influenza A virus genome is contained on eight single (non-paired) RNA strands that code for eleven proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2). The total genome size is 13,588 bases. The segmented nature of the genome allows for the exchange of entire genes between different viral strains
during cellular cohabitation. The eight RNA segments are:
The genome segments have common terminal sequences, and the ends of the RNA strands are partially complementary
, allowing them to bond to each other by hydrogen bond
s. After transcription from negative-sense to positive-sense RNA
the +RNA strands get the cellular 5' cap
added by cap snatching, which involves the viral protein NS1 binding to the cellular pre-mRNAs. The cap is then cleaved from the cellular pre-mRNA using a second viral protein, PA. The short oligo
cap is then added to the influenza +RNA strands, allowing its processing as messenger RNA
by ribosome
s. The +RNA strands also serve for synthesis of -RNA strands for new virions.
The RNA
synthesis and its assembly with the nucleoprotein takes place in the cell nucleus
, the synthesis of proteins takes place in the cytoplasm
. The assembled virion cores leave the nucleus and migrate towards the cell membrane
, with patches of viral transmembrane protein
s (hemagglutinin, neuraminidase and M2 proteins) and an underlying layer of the M1 protein, and bud
through these patches, releasing finished enveloped viruses into the extracellular fluid
.
Evidence has been found for the presence of RNA structure
in Influenza A virus. Structured RNA appears to be favored in the +RNA, and is clustered near regions with functional importance. Two pseudoknot
RNA structures were predicted that include the 3' splice site in Segments 7 and 8, which are both alternatively spliced to produce the M2 and NEP proteins respectively. Towards the 5' splice sites of these mRNAs, hairpin loop and multibranch loop structures were predicted. As well as these structures near splice sites, a pseudoknot
was proposed in Segment 2, which encompasses the start codon
for an internally transcribed open reading frame
for a small polypeptide product (PB1-F2).
Avian influenza
Fowl
act as natural asymptomatic carrier
s of Influenza A viruses. Prior to the current H5N1 epizootic, strains of Influenza A virus had been demonstrated to be transmitted from wild fowl to only birds, pigs, horse
s, seal
s, whale
s and humans; and only between humans and pigs and between humans and domestic fowl; and not other pathways such as domestic fowl to horse.
Wild aquatic birds are the natural hosts for a large variety of influenza A viruses. Occasionally viruses are transmitted from these birds to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics.
H5N1 has been shown to be transmitted to tigers, leopards, and domestic cats that were fed uncooked domestic fowl (chickens) with the virus. H3N8 viruses from horses have crossed over and caused outbreaks in dog
s. Laboratory mice have been infected successfully with a variety of avian flu genotypes.
Influenza A viruses spread in the air and in manure
and survives longer in cold weather. It can also be transmitted by contaminated feed, water, equipment and clothing; however, there is no evidence that the virus can survive in well-cooked meat. Symptoms in animals vary, but virulent strains can cause death within a few days.
"Highly pathogenic avian influenza virus is on every top ten list available for potential agricultural bioweapon agents".
Avian influenza viruses that the OIE and others test for in order to control poultry disease include: H5N1
, H7N2
, H1N7, H7N3
, H13N6, H5N9
, H11N6, H3N8
, H9N2
, H5N2
, H4N8, H10N7
, H2N2
, H8N4, H14N5, H6N5, H12N5 and others.
Known outbreaks of highly pathogenic flu in poultry 1959-2003
1979: "More than 400 harbor seals, most of them immature, died along the New England coast between December 1979 and October 1980 of acute pneumonia associated with influenza virus, A/Seal/Mass/1/180 (H7N7)."
1995: "[V]accinated birds can develop asymptomatic infections that allow virus to spread, mutate, and recombine (ProMED-mail, 2004j). Intensive surveillance is required to detect these “silent epidemics” in time to curtail them. In Mexico, for example, mass vaccination of chickens against epidemic H5N2 influenza in 1995 has had to continue in order to control a persistent and evolving virus (Lee et al., 2004)."
1997: "Influenza A viruses normally seen in one species sometimes can cross over and cause illness in another species. For example, until 1997, only H1N1 viruses circulated widely in the U.S. pig population. However, in 1997, H3N2 viruses from humans were introduced into the pig population and caused widespread disease among pigs. Most recently, H3N8 viruses from horses have crossed over and caused outbreaks in dogs."
2000: "In California
, poultry
producers kept their knowledge of a recent H6N2 avian influenza outbreak to themselves due to their fear of public rejection of poultry products; meanwhile, the disease spread across the western United States and has since become endemic."
2003: In Netherlands H7N7 influenza virus infection broke out in poultry on several farms.
2004: In North America
, the presence of avian influenza strain H7N3 was confirmed at several poultry farms in British Columbia
in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus.
2005: Tens of millions of birds died of H5N1 influenza and hundreds of millions of birds were culled to protect humans from H5N1. H5N1 is endemic in birds in southeast Asia and represents a long term pandemic threat.
2006: H5N1 spreads across the globe killing hundreds of millions of birds and over 100 people causing a significant H5N1 impact from both actual deaths and predicted possible deaths.
Swine flu
Horse flu
Dog flu
H3N8
"Human influenza virus" usually refers to those subtypes that spread widely among humans. H1N1, H1N2, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans.
Genetic factors in distinguishing between "human flu viruses" and "avian influenza viruses" include:
"About 52 key genetic changes distinguish avian influenza strains from those that spread easily among people, according to researchers in Taiwan, who analyzed the genes of more than 400 A type flu viruses." "How many mutations would make an avian virus capable of infecting humans efficiently, or how many mutations would render an influenza virus a pandemic strain, is difficult to predict. We have examined sequences from the 1918 strain, which is the only pandemic influenza virus that could be entirely derived from avian strains. Of the 52 species-associated positions, 16 have residues typical for human strains; the others remained as avian signatures. The result supports the hypothesis that the 1918 pandemic virus is more closely related to the avian influenza A virus than are other human influenza viruses."
Human flu symptoms usually include fever
, cough
, sore throat
, muscle aches
, conjunctivitis
and, in severe cases, severe breathing problems and pneumonia
that may be fatal. The severity of the infection will depend to a large part on the state of the infected person's immune system
and if the victim has been exposed to the strain before, and is therefore partially immune.
Highly pathogenic H5N1 avian influenza in a human is far worse, killing 50% of humans that catch it. In one case, a boy with H5N1 experienced diarrhea
followed rapidly by a coma
without developing respiratory or flu-like symptoms.
The Influenza A virus subtypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:
H1N1
H2N2
H3N2
H5N1
H7N7
H1N2
H9N2
H7N2
H7N3
H5N2
H10N7
Taubenberger says:
Researchers from the National Institutes of Health
used data from the Influenza Genome Sequencing Project
and concluded that during the ten-year period examined most of the time the hemagglutinin gene in H3N2 showed no significant excess of mutations in the antigenic regions while an increasing variety of strains accumulated. This resulted in one of the variants eventually achieving higher fitness, becoming dominant, and in a brief interval of rapid evolution
rapidly sweeping through the population and eliminating most other variants.
Short-term Evolution
In the short-term evolution of influenza A virus, a 2006 study found that stochastic, or random, processes are key factors. Influenza A virus HA antigenic evolution appears to be characterized more by punctuated, sporadic jumps as opposed to a constant rate of antigenic change . Using phylogenetic analysis of 413 complete genomes of human influenza A viruses that were collected throughout the state of New York, the authors of Nelson et al. 2006 were able to show that genetic diversity, and not antigenic drift, shaped the short-term evolution of influenza A via random migration and reassortment. The evolution of these viruses is dominated more by the random importation of genetically different viral strains from other geographic locations and less by natural selection. Within a given season, adaptive evolution is infrequent and had an overall weak effect as evidenced from the data gathered from the 413 genomes. Phylogenetic analysis revealed the different strains were derived from newly imported genetic material as opposed to isolates that had been circulating in New York in previous seasons. Therefore, the gene flow in and out of this population, and not natural selection, was more important in the short term.
General information
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
in bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s and some mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s and is the only species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...
of Influenzavirus A. Influenzavirus A is a genus
Genus
In biology, a genus is a low-level taxonomic rank used in the biological classification of living and fossil organisms, which is an example of definition by genus and differentia...
of the Orthomyxoviridae
Orthomyxoviridae
The Orthomyxoviridae are a family of RNA viruses that includes five genera: Influenzavirus A, Influenzavirus B, Influenzavirus C, Isavirus and Thogotovirus. A sixth has recently been described...
family of virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon. Some isolates
Primary isolate
Primary isolate is a pure microbial or viral sample that has been obtained from an infected individual, rather than grown in a laboratory. In chemistry and bacteriology, the verb isolate means to obtain a pure chemical, bacteriological or viral sample...
of influenza A virus cause severe disease both in domestic poultry and, rarely, in human
Human
Humans are the only living species in the Homo genus...
s. Occasionally viruses are transmitted from wild aquatic birds to domestic poultry and this may cause an outbreak or give rise to human influenza pandemic
Pandemic
A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...
s.
Influenza A viruses are negative sense
Sense (molecular biology)
In molecular biology and genetics, sense is a concept used to compare the polarity of nucleic acid molecules, such as DNA or RNA, to other nucleic acid molecules...
, single-stranded, segmented RNA virus
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...
es.
There are several subtypes, labeled according to an H number (for the type of hemagglutinin) and an N number (for the type of neuraminidase
Viral neuraminidase
Viral neuraminidase is a type of neuraminidase found on the surface of influenza viruses that enables the virus to be released from the host cell...
). There are 16 different H antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s (H1 to H16) and nine different N antigens (N1 to N9). The newest H type (H16) was isolated from black-headed gull
Black-headed Gull
The Black-headed Gull is a small gull which breeds in much of Europe and Asia, and also in coastal eastern Canada. Most of the population is migratory, wintering further south, but some birds in the milder westernmost areas of Europe are resident...
s caught in Sweden
Sweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
and the Netherlands
Netherlands
The Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
in 1999 and reported in the literature in 2005.
Each virus subtype has mutate
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
d into a variety of strains with differing pathogen
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
ic profiles; some pathogenic to one species but not others, some pathogenic to multiple species.
A filtered and purified influenza A vaccine for humans was developed and many countries have stockpiled it to allow a quick administration to the population in the event of an avian influenza pandemic. Avian influenza is sometimes called avian flu, and commonly bird flu. In 2011, researchers reported the discovery of an antibody effective against all types of the influenza A virus.
Variants and subtypes
Influenza type A viruses are categorized into subtypes based on the type of two proteins on the surface of the viral envelope:- H = hemagglutininHemagglutininInfluenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
, a protein that causes red blood cells to agglutinate. - N = neuraminidaseNeuraminidaseNeuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...
, an enzyme that cleaves the glycosidic linkages of the monosaccharideMonosaccharideMonosaccharides are the most basic units of biologically important carbohydrates. They are the simplest form of sugar and are usually colorless, water-soluble, crystalline solids. Some monosaccharides have a sweet taste. Examples of monosaccharides include glucose , fructose , galactose, xylose...
, neuraminic acidNeuraminic acidNeuraminic acid is a 9-carbon monosaccharide, a derivative of a ketononose. Neuraminic acid may be visualized as the product of an aldol-condensation product of pyruvic acid and D-mannosamine...
Different influenza viruses encode for different hemagglutinin and neuraminidase proteins. For example, the H5N1 virus designates an influenza A subtype that has a type 5 hemagglutinin (H) protein and a type 1 neuraminidase (N) protein. There are 16 known types of hemagglutinin and 9 known types of neuraminidase, so, in theory, 144 different combinations of these proteins are possible.
Some variants are identified and named according to the isolate that they are like and thus are presumed to share lineage (example Fujian flu
Fujian flu
Fujian flu refers to flu caused by either a Fujian human flu strain of the H3N2 subtype of the Influenza A virus or a Fujian bird flu strain of the H5N1 subtype of the Influenza A virus...
virus like); according to their typical host (example human flu
Human flu
Human flu is a term used to refer to influenza cases caused by Orthomyxoviridae that are endemic to human populations . It is an arbitrary categorization scheme, and is not associated with phylogenetics-based taxonomy...
virus); according to their subtype (example H3N2); and according to their deadliness (example LP, Low Pathogenic). So a flu from a virus similar to the isolate A/Fujian/411/2002(H3N2) is called Fujian
Fujian
' , formerly romanised as Fukien or Huguing or Foukien, is a province on the southeast coast of mainland China. Fujian is bordered by Zhejiang to the north, Jiangxi to the west, and Guangdong to the south. Taiwan lies to the east, across the Taiwan Strait...
flu, human flu, and H3N2 flu.
Variants are sometimes named according to the species (host) the strain is endemic in or adapted to. The main variants named using this convention are:
- Bird flu
- Human fluHuman fluHuman flu is a term used to refer to influenza cases caused by Orthomyxoviridae that are endemic to human populations . It is an arbitrary categorization scheme, and is not associated with phylogenetics-based taxonomy...
- Swine influenza
- Equine influenza
- Canine influenzaCanine influenzaCanine influenza is influenza occurring in canines. Canine influenza is caused by varieties of Influenzavirus A, such as equine influenza virus H3N8, which in 2004 was discovered to cause disease in dogs. Because of the lack of previous exposure to this virus, dogs have no natural immunity to...
Variants have also sometimes been named according to their deadliness in poultry, especially chickens:
- Low Pathogenic Avian Influenza (LPAI)
- Highly Pathogenic Avian Influenza (HPAI), also called: deadly flu or death flu
Most known strains are extinct strains. For example, the annual flu subtype H3N2 no longer contains the strain that caused the Hong Kong flu
Hong Kong flu
The Hong Kong flu was a category 2 flu pandemic whose outbreak in 1968 and 1969 killed an estimated one million people worldwide. It was caused by an H3N2 strain of the influenza A virus, descended from H2N2 through antigenic shift, a genetic process in which genes from multiple subtypes reassorted...
.
Annual flu
The annual flu (also called "seasonal flu" or "human flu")in the U.S. "results in approximately 36,000 deaths and more than 200,000 hospitalizations each year. In addition to this human toll, influenza is annually responsible for a total cost of over $10 billion in the U.S.".
The annually updated trivalent influenza vaccine consists of hemagglutinin
Hemagglutinin
Influenza hemagglutinin or haemagglutinin is a type of hemagglutinin found on the surface of the influenza viruses. It is an antigenic glycoprotein. It is responsible for binding the virus to the cell that is being infected...
(HA) surface glycoprotein components from influenza H3N2, H1N1, and B influenza
Influenzavirus B
Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".Influenza B viruses are only known to infect humans and seals, giving them influenza...
viruses.
Measured resistance to the standard antiviral drugs amantadine
Amantadine
Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...
and rimantadine
Rimantadine
Rimantadine is an orally administered antiviral drug used to treat, and in rare cases prevent, influenzavirus A infection. When taken within one to two days of developing symptoms, rimantadine can shorten the duration and moderate the severity of influenza. Both rimantadine and the similar drug...
in H3N2 has increased from 1% in 1994 to 12% in 2003 to 91% in 2005.
"[C]ontemporary human H3N2 influenza viruses are now endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
in pig
Pig
A pig is any of the animals in the genus Sus, within the Suidae family of even-toed ungulates. Pigs include the domestic pig, its ancestor the wild boar, and several other wild relatives...
s in southern China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
and can reassort
Reassortment
Reassortment is the mixing of the genetic material of a species into new combinations in different individuals. Several different processes contribute to reassortment, including assortment of chromosomes, and chromosomal crossover. It is particularly used when two similar viruses that are infecting...
with avian H5N1 viruses in this intermediate host." "H5N1 virus is now endemic in poultry in Asia (Table 2-1) and has gained an entrenched ecological niche from which to present a long-term pandemic threat to humans. At present, these viruses are poorly transmitted from poultry to humans, and there is no conclusive evidence of human-to-human transmission. However, continued, extensive exposure of the human population to H5N1 viruses increases the likelihood that the viruses will acquire the necessary characteristics for efficient human-to-human transmission through genetic mutation or reassortment with a prevailing human influenza A virus. Furthermore, contemporary human H3N2 influenza viruses are now endemic in pigs in southern China (Peiris et al., 2001) and can reassort with avian H5N1 viruses in this 'intermediate host.' Therefore, it is imperative that outbreaks of H5N1 disease in poultry in Asia are rapidly and sustainably controlled. The seasonality of the disease in poultry, together with the control measures already implemented, are likely to reduce temporarily the frequency of H5N1 influenza outbreaks and the probability of human infection."
F16 antibody
F16, an antibodyAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
that targets the hemagglutinin protein, was recently discovered and is the only known antibody effective against all 16 subtypes of the influenza A virus.
Structure and genetics
"The physical structure of all influenza A viruses is similar. The virions or virus particles are enveloped and can be either spherical or filamentous in form. In clinical isolates that have undergone limited passages in eggs or tissue culture, there are more filamentous than spherical particles, whereas passaged laboratory strains consist mainly of spherical virions."The Influenza A virus genome is contained on eight single (non-paired) RNA strands that code for eleven proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2). The total genome size is 13,588 bases. The segmented nature of the genome allows for the exchange of entire genes between different viral strains
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...
during cellular cohabitation. The eight RNA segments are:
- HA encodes hemagglutinin (about 500 molecules of hemagglutinin are needed to make one virion) "The extent of infection into host organism is determined by HA. Influenza viruses bud from the apical surface of polarized epithelial cells (e.g. bronchial epithelial cells) into lumen of lungs and are therefore usually pneumotropic. The reason is that HA is cleaved by tryptase clara which is restricted to lungs. However HAs of H5 and H7 pantropic avian viruses subtypes can be cleaved by furin and subtilisin-type enzymes, allowing the virus to grow in other organs than lungs."
- NA encodes neuraminidaseNeuraminidaseNeuraminidase enzymes are glycoside hydrolase enzymes that cleave the glycosidic linkages of neuraminic acids. Neuraminidase enzymes are a large family, found in a range of organisms. The most commonly known neuraminidase is the viral neuraminidase, a drug target for the prevention of the spread...
(about 100 molecules of neuraminidase are needed to make one virion). - NP encodes nucleoproteinNucleoproteinA nucleoprotein is any protein that is structurally associated with nucleic acid .Many viruses harness this protein, and they are known for being host-specific...
. - M encodes two matrix proteinMatrix proteinViral matrix proteins are non structural proteins linking the viral envelope with the virus core. They play a crucial role in virus assembly, and interact with the RNP complex as well as with the viral membrane...
s (the M1M1 proteinThe M1 protein is a matrix protein of the influenza virus. It forms a coat inside the viral envelope.The M1 protein binds to the viral RNA. The binding is not specific to any RNA sequence, and is performed via a peptide sequence rich in basic amino acids....
and the M2M2 proteinThe M2 protein is a proton-selective ion channel protein, integral in the viral envelope of the influenza A virus. The channel itself is a homotetramer , where the units are helices stabilized by two disulfide bonds...
) by using different reading frameReading frameIn biology, a reading frame is a way of breaking a sequence of nucleotides in DNA or RNA into three letter codons which can be translated in amino acids. There are 3 possible reading frames in an mRNA strand: each reading frame corresponding to starting at a different alignment...
s from the same RNA segment (about 3000 matrix protein molecules are needed to make one virion). - NS encodes two distinct non-structural proteins (NS1 and NEP) by using different reading frames from the same RNA segment.
- PA encodes an RNA polymeraseRNA polymeraseRNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
. - PB1 encodes an RNA polymerase and PB1-F2 protein (induces apoptosisApoptosisApoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
) by using different reading frames from the same RNA segment. - PB2 encodes an RNA polymerase.
The genome segments have common terminal sequences, and the ends of the RNA strands are partially complementary
Complementarity (molecular biology)
In molecular biology, complementarity is a property of double-stranded nucleic acids such as DNA, as well as DNA:RNA duplexes. Each strand is complementary to the other in that the base pairs between them are non-covalently connected via two or three hydrogen bonds...
, allowing them to bond to each other by hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...
s. After transcription from negative-sense to positive-sense RNA
Sense (molecular biology)
In molecular biology and genetics, sense is a concept used to compare the polarity of nucleic acid molecules, such as DNA or RNA, to other nucleic acid molecules...
the +RNA strands get the cellular 5' cap
5' cap
The 5' cap is a specially altered nucleotide on the 5' end of precursor messenger RNA and some other primary RNA transcripts as found in eukaryotes. The process of 5' capping is vital to creating mature messenger RNA, which is then able to undergo translation...
added by cap snatching, which involves the viral protein NS1 binding to the cellular pre-mRNAs. The cap is then cleaved from the cellular pre-mRNA using a second viral protein, PA. The short oligo
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
cap is then added to the influenza +RNA strands, allowing its processing as messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
by ribosome
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
s. The +RNA strands also serve for synthesis of -RNA strands for new virions.
The RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
synthesis and its assembly with the nucleoprotein takes place in the cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, the synthesis of proteins takes place in the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
. The assembled virion cores leave the nucleus and migrate towards the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
, with patches of viral transmembrane protein
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
s (hemagglutinin, neuraminidase and M2 proteins) and an underlying layer of the M1 protein, and bud
Budding
Budding is a form of asexual reproduction in which a new organism grows on another one. The new organism remains attached as it grows, separating from the parent organism only when it is mature. Since the reproduction is asexual, the newly created organism is a clone and is genetically identical...
through these patches, releasing finished enveloped viruses into the extracellular fluid
Extracellular fluid
Extracellular fluid usually denotes all body fluid outside of cells. The remainder is called intracellular fluid.In some animals, including mammals, the extracellular fluid can be divided into two major subcompartments, interstitial fluid and blood plasma...
.
Evidence has been found for the presence of RNA structure
RNA structure
Biomolecular structure is the structure of biomolecules, mainly proteins and the nucleic acids DNA and RNA. The structure of these molecules is frequently decomposed into primary structure, secondary structure, tertiary structure, and quaternary structure. The scaffold for this structure is...
in Influenza A virus. Structured RNA appears to be favored in the +RNA, and is clustered near regions with functional importance. Two pseudoknot
Pseudoknot
A pseudoknot is a nucleic acid secondary structure containing at least two stem-loop structures in which half of one stem is intercalated between the two halves of another stem. The pseudoknot was first recognized in the turnip yellow mosaic virus in 1982...
RNA structures were predicted that include the 3' splice site in Segments 7 and 8, which are both alternatively spliced to produce the M2 and NEP proteins respectively. Towards the 5' splice sites of these mRNAs, hairpin loop and multibranch loop structures were predicted. As well as these structures near splice sites, a pseudoknot
Pseudoknot
A pseudoknot is a nucleic acid secondary structure containing at least two stem-loop structures in which half of one stem is intercalated between the two halves of another stem. The pseudoknot was first recognized in the turnip yellow mosaic virus in 1982...
was proposed in Segment 2, which encompasses the start codon
Start codon
The start codon is generally defined as the point, sequence, at which a ribosome begins to translate a sequence of RNA into amino acids.When an RNA transcript is "read" from the 5' carbon to the 3' carbon by the ribosome the start codon is the first codon on which the tRNA bound to Met,...
for an internally transcribed open reading frame
Open reading frame
In molecular genetics, an open reading frame is a DNA sequence that does not contain a stop codon in a given reading frame.Normally, inserts which interrupt the reading frame of a subsequent region after the start codon cause frameshift mutation of the sequence and dislocate the sequences for stop...
for a small polypeptide product (PB1-F2).
In nonhumans
- See H5N1H5N1Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
for the current epizooticEpizooticIn epizoology, an epizootic is a disease that appears as new cases in a given animal population, during a given period, at a rate that substantially exceeds what is "expected" based on recent experience . Epidemic is the analogous term applied to human populations...
(an epidemicEpidemicIn epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...
in nonhumans) and panzootic (a disease affecting animals of many species especially over a wide area) of H5N1 influenza
Avian influenza
Fowl
Fowl
Fowl is a word for birds in general but usually refers to birds belonging to one of two biological orders, namely the gamefowl or landfowl and the waterfowl...
act as natural asymptomatic carrier
Asymptomatic carrier
An asymptomatic carrier is a person or other organism that has contracted an infectious disease, but who displays no symptoms. Although unaffected by the disease themselves, carriers can transmit it to others...
s of Influenza A viruses. Prior to the current H5N1 epizootic, strains of Influenza A virus had been demonstrated to be transmitted from wild fowl to only birds, pigs, horse
Horse
The horse is one of two extant subspecies of Equus ferus, or the wild horse. It is a single-hooved mammal belonging to the taxonomic family Equidae. The horse has evolved over the past 45 to 55 million years from a small multi-toed creature into the large, single-toed animal of today...
s, seal
Pinniped
Pinnipeds or fin-footed mammals are a widely distributed and diverse group of semiaquatic marine mammals comprising the families Odobenidae , Otariidae , and Phocidae .-Overview: Pinnipeds are typically sleek-bodied and barrel-shaped...
s, whale
Whale
Whale is the common name for various marine mammals of the order Cetacea. The term whale sometimes refers to all cetaceans, but more often it excludes dolphins and porpoises, which belong to suborder Odontoceti . This suborder also includes the sperm whale, killer whale, pilot whale, and beluga...
s and humans; and only between humans and pigs and between humans and domestic fowl; and not other pathways such as domestic fowl to horse.
Wild aquatic birds are the natural hosts for a large variety of influenza A viruses. Occasionally viruses are transmitted from these birds to other species and may then cause devastating outbreaks in domestic poultry or give rise to human influenza pandemics.
H5N1 has been shown to be transmitted to tigers, leopards, and domestic cats that were fed uncooked domestic fowl (chickens) with the virus. H3N8 viruses from horses have crossed over and caused outbreaks in dog
Dog
The domestic dog is a domesticated form of the gray wolf, a member of the Canidae family of the order Carnivora. The term is used for both feral and pet varieties. The dog may have been the first animal to be domesticated, and has been the most widely kept working, hunting, and companion animal in...
s. Laboratory mice have been infected successfully with a variety of avian flu genotypes.
Influenza A viruses spread in the air and in manure
Manure
Manure is organic matter used as organic fertilizer in agriculture. Manures contribute to the fertility of the soil by adding organic matter and nutrients, such as nitrogen, that are trapped by bacteria in the soil...
and survives longer in cold weather. It can also be transmitted by contaminated feed, water, equipment and clothing; however, there is no evidence that the virus can survive in well-cooked meat. Symptoms in animals vary, but virulent strains can cause death within a few days.
"Highly pathogenic avian influenza virus is on every top ten list available for potential agricultural bioweapon agents".
Avian influenza viruses that the OIE and others test for in order to control poultry disease include: H5N1
H5N1
Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
, H7N2
H7N2
H7N2 is a subtype of the species Influenza A virus .A CDC study following outbreaks of H7N2 in commercial poultry farms in western Virginia in 2002 concluded:...
, H1N7, H7N3
H7N3
H7N3 is a subtype of the species Influenza A virus .In North America, the presence of H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans infected with it have been...
, H13N6, H5N9
H5N9
H5N9 is a subtype of the species Influenza A virus .A highly pathogenic strain of H5N9 caused a minor flu outbreak in 1966 in Ontario and Manitoba, Canada in turkeys....
, H11N6, H3N8
H3N8
H3N8 is a subtype of the species Influenza A virus that is endemic in birds, horses and dogs.-Introduction:Equine influenza is a highly contagious respiratorydisease of horses and related animals such as donkeys,...
, H9N2
H9N2
H9N2 is a subtype of the species Influenza A virus ."H9N2 influenza viruses of domestic ducks have become established in the domestic poultry of Asia. Phylogenetic and antigenic analyses of the H9N2 viruses isolated from Hong Kong markets suggest three distinct sublineages...
, H5N2
H5N2
H5N2 is a subtype of the species Influenzavirus A .-H5N2 and birds:Low pathogenic avian inluenza H5N2 virus in poultry later gained accentuated virulence in the United States and Mexico...
, H4N8, H10N7
H10N7
H10N7 is a subtype of the species Influenza A virus . In 2004 in Egypt, H10N7 was reported for the first time in humans. It caused illness in two one-year old infants, residents of Ismaillia, Egypt; one child’s father a poultry merchant.The first reported H10N7 outbreak in the US occurred in...
, H2N2
H2N2
H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds...
, H8N4, H14N5, H6N5, H12N5 and others.
Known outbreaks of highly pathogenic flu in poultry 1959-2003
| Year | Area | Affected | Subtype |
|---|---|---|---|
| 1959 | Scotland | chicken | H5N1 H5N1 Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species... |
| 1963 | England | turkey | H7N3 H7N3 H7N3 is a subtype of the species Influenza A virus .In North America, the presence of H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans infected with it have been... |
| 1966 | Ontario (Canada) | turkey | H5N9 H5N9 H5N9 is a subtype of the species Influenza A virus .A highly pathogenic strain of H5N9 caused a minor flu outbreak in 1966 in Ontario and Manitoba, Canada in turkeys.... |
| 1976 | Victoria (Australia) | chicken | H7N7 H7N7 H7N7 is a subtype of Influenzavirus A, a genus of Orthomyxovirus, the viruses responsible for influenza. Highly pathogenic strains and low pathogenic strains exist. H7N7 can infect humans, birds, pigs, seals, and horses in the wild; and has infected mice in laboratory studies... |
| 1979 | Germany | chicken | H7N7 |
| 1979 | England | turkey | H7N7 |
| 1983 | Pennsylvania (USA)* | chicken, turkey | H5N2 H5N2 H5N2 is a subtype of the species Influenzavirus A .-H5N2 and birds:Low pathogenic avian inluenza H5N2 virus in poultry later gained accentuated virulence in the United States and Mexico... |
| 1983 | Ireland | turkey | H5N8 H5N8 H5N8 is a subtype of the species Influenza A virus .A highly pathogenic strain of it called A/turkey/Ireland/1378/83 caused a minor flu outbreak in 1983 in Ireland in turkeys.... |
| 1985 | Victoria (Australia) | chicken | H7N7 |
| 1991 | England | turkey | H5N1 |
| 1992 | Victoria (Australia) | chicken | H7N3 |
| 1994 | Queensland (Australia) | chicken | H7N3 |
| 1994 | Mexico* | chicken | H5N2 |
| 1994 | Pakistan* | chicken | H7N3 |
| 1997 | New South Wales (Australia) | chicken | H7N4 H7N4 H7N4 is a subtype of the species Influenza A virus .A highly pathogenic strain of it caused a minor flu outbreak in 1997 in New South Wales, Australia in chicken.... |
| 1997 | Hong Kong (China)* | chicken | H5N1 |
| 1997 | Italy | chicken | H5N2 |
| 1999 | Italy* | turkey | H7N1 H7N1 H7N1 is a subtype of the species Influenza A virus .A highly pathogenic strain of it caused a flu outbreak with significant spread to numerous farms, resulting in great economic losses in 1999 in Italy in turkeys.... |
| 2002 | Hong Kong (China) | chicken | H5N1 |
| 2002 | Chile | chicken | H7N3 |
| 2003 | Netherlands* | chicken | H7N7 |
*Outbreaks with significant spread to numerous farms, resulting in great economic losses. Most other outbreaks involved little or no spread from the initially infected farms. |
|||
1979: "More than 400 harbor seals, most of them immature, died along the New England coast between December 1979 and October 1980 of acute pneumonia associated with influenza virus, A/Seal/Mass/1/180 (H7N7)."
1995: "[V]accinated birds can develop asymptomatic infections that allow virus to spread, mutate, and recombine (ProMED-mail, 2004j). Intensive surveillance is required to detect these “silent epidemics” in time to curtail them. In Mexico, for example, mass vaccination of chickens against epidemic H5N2 influenza in 1995 has had to continue in order to control a persistent and evolving virus (Lee et al., 2004)."
1997: "Influenza A viruses normally seen in one species sometimes can cross over and cause illness in another species. For example, until 1997, only H1N1 viruses circulated widely in the U.S. pig population. However, in 1997, H3N2 viruses from humans were introduced into the pig population and caused widespread disease among pigs. Most recently, H3N8 viruses from horses have crossed over and caused outbreaks in dogs."
2000: "In California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...
, poultry
Poultry
Poultry are domesticated birds kept by humans for the purpose of producing eggs, meat, and/or feathers. These most typically are members of the superorder Galloanserae , especially the order Galliformes and the family Anatidae , commonly known as "waterfowl"...
producers kept their knowledge of a recent H6N2 avian influenza outbreak to themselves due to their fear of public rejection of poultry products; meanwhile, the disease spread across the western United States and has since become endemic."
2003: In Netherlands H7N7 influenza virus infection broke out in poultry on several farms.
2004: In North America
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
, the presence of avian influenza strain H7N3 was confirmed at several poultry farms in British Columbia
British Columbia
British Columbia is the westernmost of Canada's provinces and is known for its natural beauty, as reflected in its Latin motto, Splendor sine occasu . Its name was chosen by Queen Victoria in 1858...
in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus.
2005: Tens of millions of birds died of H5N1 influenza and hundreds of millions of birds were culled to protect humans from H5N1. H5N1 is endemic in birds in southeast Asia and represents a long term pandemic threat.
2006: H5N1 spreads across the globe killing hundreds of millions of birds and over 100 people causing a significant H5N1 impact from both actual deaths and predicted possible deaths.
Swine flu
- Swine influenza (or "pig influenza") refers to a subset of Orthomyxoviridae that create influenza in pigs and are endemic in pigs. The species of Orthomyxoviridae that can cause flu in pigs are Influenza A virus and Influenza C virusInfluenzavirus CInfluenzavirus C is a genus in the virus family Orthomyxoviridae, which includes those viruses which cause influenza. The only species in this genus is called "Influenza C virus".Influenza C viruses are known to infect humans and pigs, giving them influenza...
but not all genotypes of these two species infect pigs. The known subtypes of Influenza A virus that create influenza in pigs and are endemic in pigs are H1N1, H1N2, H3N1Influenza A virus subtype H3N1H3N1 is a subtype of the species Influenza A virus, mostly affecting pigs.The known subtypes of Influenza A virus that create influenza in pigs and are endemic in pigs are H1N1, H1N2, H3N1 and H3N2.-See also:strains named by isolate*Fujian flu...
and H3N2.
Horse flu
- Horse flu (or "Equine influenza") refers to varieties of Influenza A virus that affect horses. Horse 'flu viruses were only isolated in 1956. There are two main types of virus called equine-1 (H7N7) which commonly affects horse heart muscle and equine-2 (H3N8) which is usually more severe.
Dog flu
- Dog flu (or "canine influenza") refers to varieties of Influenza A virus that affect dogs. The equine influenza virus H3N8 was found to infect and kill - with respiratory illness - greyhound race dogs at a Florida racetrack in January 2004.
H3N8
- H3N8 is now endemic in birds, horses and dogs.
Human influenza virus
Genetic factors in distinguishing between "human flu viruses" and "avian influenza viruses" include:
- PB2: (RNA polymerase): Amino acidAmino acidAmino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
(or residueResidue (chemistry)In chemistry, residue is the material remaining after a distillation or an evaporation, or to a portion of a larger molecule, such as a methyl group. It may also refer to the undesired byproducts of a reaction....
) position 627 in the PB2 protein encoded by the PB2 RNA gene. Until H5N1, all known avian influenza viruses had a GluGlutamic acidGlutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
at position 627, while all human influenza viruses had a lysineLysineLysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
. - HA: (hemagglutinin): Avian influenza HA bind alpha 2-3 sialic acidSialic acidSialic acid is a generic term for the N- or O-substituted derivatives of neuraminic acid, a monosaccharide with a nine-carbon backbone. It is also the name for the most common member of this group, N-acetylneuraminic acid...
receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors.
"About 52 key genetic changes distinguish avian influenza strains from those that spread easily among people, according to researchers in Taiwan, who analyzed the genes of more than 400 A type flu viruses." "How many mutations would make an avian virus capable of infecting humans efficiently, or how many mutations would render an influenza virus a pandemic strain, is difficult to predict. We have examined sequences from the 1918 strain, which is the only pandemic influenza virus that could be entirely derived from avian strains. Of the 52 species-associated positions, 16 have residues typical for human strains; the others remained as avian signatures. The result supports the hypothesis that the 1918 pandemic virus is more closely related to the avian influenza A virus than are other human influenza viruses."
Human flu symptoms usually include fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
, sore throat
Sore throat
A sore throat or throat pain is a common physical symptom usually caused by acute pharyngitis, or throat inflammation, though it also occurs in a number of other situations, such as post trauma and in diphtheria. It can cause mild to extreme pain....
, muscle aches
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
, conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...
and, in severe cases, severe breathing problems and pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
that may be fatal. The severity of the infection will depend to a large part on the state of the infected person's immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
and if the victim has been exposed to the strain before, and is therefore partially immune.
Highly pathogenic H5N1 avian influenza in a human is far worse, killing 50% of humans that catch it. In one case, a boy with H5N1 experienced diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
followed rapidly by a coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
without developing respiratory or flu-like symptoms.
The Influenza A virus subtypes that have been confirmed in humans, ordered by the number of known human pandemic deaths, are:
- H1N1H1N1'Influenza A virus is a subtype of influenza A virus and was the most common cause of human influenza in 2009. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a small fraction of all seasonal influenza. H1N1 strains caused a few percent of...
caused "Spanish FluSpanish fluThe 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...
" and the 2009 swine flu outbreak - H2N2H2N2H2N2 is a subtype of the type influenzavirus A. H2N2 has mutated into various strains including the Asian flu strain , H3N2, and various strains found in birds...
caused "Asian FluAsian fluAsian Flu may refer to:* The Asian Financial Crisis of 1997, or* Asian Flu, the H2N2 virus...
" in the late 1950s - H3N2H3N2Influenza A virus subtype H3N2 is a subtype of viruses that cause influenza . H3N2 Viruses can infect birds and mammals. In birds, humans, and pigs, the virus has mutated into many strains...
caused "Hong Kong FluHong Kong fluThe Hong Kong flu was a category 2 flu pandemic whose outbreak in 1968 and 1969 killed an estimated one million people worldwide. It was caused by an H3N2 strain of the influenza A virus, descended from H2N2 through antigenic shift, a genetic process in which genes from multiple subtypes reassorted...
" in the late 1960s - H5N1H5N1Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
considered a global influenza pandemicInfluenza pandemicAn influenza pandemic is an epidemic of an influenza virus that spreads on a worldwide scale and infects a large proportion of the human population. In contrast to the regular seasonal epidemics of influenza, these pandemics occur irregularly, with the 1918 Spanish flu the most serious pandemic in...
threat through its spreadGlobal spread of H5N1The global spread of highly pathogenic H5N1 influenza in birds is considered a significant pandemic threat.While other H5N1 influenza strains are known, they are significantly different from a current, highly pathogenic H5N1 strain on a genetic level, making the global spread of this new strain...
in the mid-2000s - H7N7H7N7H7N7 is a subtype of Influenzavirus A, a genus of Orthomyxovirus, the viruses responsible for influenza. Highly pathogenic strains and low pathogenic strains exist. H7N7 can infect humans, birds, pigs, seals, and horses in the wild; and has infected mice in laboratory studies...
has unusual zoonotic potential - H1N2H1N2H1N2 is a subtype of the species Influenza A virus . It is currently pandemic in both human and pig populations.H1N1, H1N2, and H3N2 are the only known Influenza A virus subtypes currently circulating among humans....
is currently endemic in humans and pigs - H9N2H9N2H9N2 is a subtype of the species Influenza A virus ."H9N2 influenza viruses of domestic ducks have become established in the domestic poultry of Asia. Phylogenetic and antigenic analyses of the H9N2 viruses isolated from Hong Kong markets suggest three distinct sublineages...
, H7N2H7N2H7N2 is a subtype of the species Influenza A virus .A CDC study following outbreaks of H7N2 in commercial poultry farms in western Virginia in 2002 concluded:...
, H7N3H7N3H7N3 is a subtype of the species Influenza A virus .In North America, the presence of H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans infected with it have been...
, H5N2H5N2H5N2 is a subtype of the species Influenzavirus A .-H5N2 and birds:Low pathogenic avian inluenza H5N2 virus in poultry later gained accentuated virulence in the United States and Mexico...
, H10N7H10N7H10N7 is a subtype of the species Influenza A virus . In 2004 in Egypt, H10N7 was reported for the first time in humans. It caused illness in two one-year old infants, residents of Ismaillia, Egypt; one child’s father a poultry merchant.The first reported H10N7 outbreak in the US occurred in...
.
H1N1
- H1N1 is currently pandemic in both human and pig populations. A variant of H1N1 was responsible for the Spanish flu pandemic that killed some 50 million to 100 million people worldwide over about a year in 1918 and 1919. Another variant was named a pandemic threat in the 2009 flu pandemic2009 flu pandemicThe 2009 flu pandemic was an influenza pandemic, and the second of the two pandemics involving H1N1 influenza virus , albeit in a new version...
. Controversy arose in October, 2005, after the H1N1 genomeGenomeIn modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
was published in the journal, ScienceScience (journal)Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....
, because of fears that this information could be used for bioterrorismBioterrorismBioterrorism is terrorism involving the intentional release or dissemination of biological agents. These agents are bacteria, viruses, or toxins, and may be in a naturally occurring or a human-modified form. For the use of this method in warfare, see biological warfare.-Definition:According to the...
.
H2N2
- The Asian Flu was a pandemic outbreak of H2N2 avian influenza that originated in China in 1957, spread worldwide that same year during which a influenza vaccine was developed, lasted until 1958 and caused between one and four million deaths.
H3N2
- H3N2 is currently endemic in both human and pig populations. It evolved from H2N2 by antigenic shiftAntigenic shiftAntigenic shift is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains...
and caused the Hong Kong Flu pandemic of 1968 and 1969 that killed up to 750,000. "An early-onset, severe form of influenza A H3N2 made headlines when it claimed the lives of several children in the United States in late 2003."
- The dominant strain of annual flu in January 2006 was H3N2. Measured resistance to the standard antiviral drugs amantadine and rimantadine in H3N2 increased from 1% in 1994 to 12% in 2003 to 91% in 2005.
- "[C]ontemporary human H3N2 influenza viruses are now endemic in pigs in southern China and can reassort with avian H5N1 viruses in this intermediate host."
H5N1
- H5N1 is the world's major influenza pandemic threat.
- "When he compared the 1918 virus with today's human flu viruses, Dr. Taubenberger noticed that it had alterations in just 25 to 30 of the virus's 4,400 amino acids. Those few changes turned a bird virus into a killer that could spread from person to person."
H7N7
- H7N7 has unusual zoonotic potential. In 2003 in Netherlands 89 people were confirmed to have H7N7 influenza virus infection following an outbreak in poultry on several farms. One death was recorded.
H1N2
- H1N2 is currently endemic in both human and pig populations. The new H1N2 strain appears to have resulted from the reassortment of the genes of the currently circulating influenza H1N1 and H3N2 subtypes. The hemagglutinin protein of the H1N2 virus is similar to that of the currently circulating H1N1 viruses and the neuraminidase protein is similar to that of the current H3N2 viruses.
H9N2
- Low pathogenic avian influenza A (H9N2) infection was confirmed in 1999, in China and Hong KongHong KongHong Kong is one of two Special Administrative Regions of the People's Republic of China , the other being Macau. A city-state situated on China's south coast and enclosed by the Pearl River Delta and South China Sea, it is renowned for its expansive skyline and deep natural harbour...
in two children, and in 2003 in Hong Kong in one child. All three fully recovered.
H7N2
- One person in New YorkNew YorkNew York is a state in the Northeastern region of the United States. It is the nation's third most populous state. New York is bordered by New Jersey and Pennsylvania to the south, and by Connecticut, Massachusetts and Vermont to the east...
in 2003 and one person in VirginiaVirginiaThe Commonwealth of Virginia , is a U.S. state on the Atlantic Coast of the Southern United States. Virginia is nicknamed the "Old Dominion" and sometimes the "Mother of Presidents" after the eight U.S. presidents born there...
in 2002 were found to have serologic evidence of infection with H7N2. Both fully recovered.
H7N3
- In North America, the presence of avian influenza strain H7N3 was confirmed at several poultry farms in British Columbia in February 2004. As of April 2004, 18 farms had been quarantined to halt the spread of the virus. Two cases of humans with avian influenza have been confirmed in that region. "Symptoms included conjunctivitis and mild influenza-like illness." Both fully recovered.
H5N2
- JapanJapanJapan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
's Health Ministry said January 2006 that poultry farm workers in Ibaraki prefecture may have been exposed to H5N2 in 2005. The H5N2 antibody titers of paired sera of 13 subjects increased fourfold or more.
H10N7
- In 2004 in EgyptEgyptEgypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...
H10N7 was reported for the first time in humans. It caused illness in two infants in Egypt. One child’s father is a poultry merchant.
Evolution
Taubenberger says:
- "All influenza A pandemics since [the Spanish flu pandemic], and indeed almost all cases of influenza A worldwide (excepting human infections from avian viruses such as H5N1 and H7N7), have been caused by descendants of the 1918 virus, including "drifted" H1N1 viruses and reassorted H2N2 and H3N2 viruses. The latter are composed of key genes from the 1918 virus, updated by subsequently incorporated avian influenza genes that code for novel surface proteins, making the 1918 virus indeed the "mother" of all pandemics.
Researchers from the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
used data from the Influenza Genome Sequencing Project
Influenza Genome Sequencing Project
The Influenza Genome Sequencing Project is an American-based genome project aimed at improving the availability of genomic sequence data from influenza viruses and related information....
and concluded that during the ten-year period examined most of the time the hemagglutinin gene in H3N2 showed no significant excess of mutations in the antigenic regions while an increasing variety of strains accumulated. This resulted in one of the variants eventually achieving higher fitness, becoming dominant, and in a brief interval of rapid evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...
rapidly sweeping through the population and eliminating most other variants.
Short-term Evolution
In the short-term evolution of influenza A virus, a 2006 study found that stochastic, or random, processes are key factors. Influenza A virus HA antigenic evolution appears to be characterized more by punctuated, sporadic jumps as opposed to a constant rate of antigenic change . Using phylogenetic analysis of 413 complete genomes of human influenza A viruses that were collected throughout the state of New York, the authors of Nelson et al. 2006 were able to show that genetic diversity, and not antigenic drift, shaped the short-term evolution of influenza A via random migration and reassortment. The evolution of these viruses is dominated more by the random importation of genetically different viral strains from other geographic locations and less by natural selection. Within a given season, adaptive evolution is infrequent and had an overall weak effect as evidenced from the data gathered from the 413 genomes. Phylogenetic analysis revealed the different strains were derived from newly imported genetic material as opposed to isolates that had been circulating in New York in previous seasons. Therefore, the gene flow in and out of this population, and not natural selection, was more important in the short term.
Further reading
Official sources- Avian influenza and Influenza Pandemics from the Centers for Disease Control and PreventionCenters for Disease Control and PreventionThe Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
- Avian influenza FAQFAQFrequently asked questions are listed questions and answers, all supposed to be commonly asked in some context, and pertaining to a particular topic. "FAQ" is usually pronounced as an initialism rather than an acronym, but an acronym form does exist. Since the acronym FAQ originated in textual...
from the World Health OrganizationWorld Health OrganizationThe World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health... - Avian influenza information from the Food and Agriculture OrganizationFood and Agriculture OrganizationThe Food and Agriculture Organization of the United Nations is a specialised agency of the United Nations that leads international efforts to defeat hunger. Serving both developed and developing countries, FAO acts as a neutral forum where all nations meet as equals to negotiate agreements and...
- U.S. Government's avian influenza information website
- European Centre for Disease Prevention and Control (ECDC) Stockholm, Sweden
General information
- "The Bird Flu and You" Full-color poster provided by the Center for Technology and National Security Policy at the National Defense UniversityNational Defense UniversityThe National Defense University is an institution of higher education funded by the United States Department of Defense, intended to facilitate high-level training, education, and the development of national security strategy. It is chartered by the Joint Chiefs of Staff, with Navy Vice Admiral...
, in collaboration with the National Security Health Policy Center - Influenza Report 2006 Online book. Research level quality information. Highly recommended.
- Special issue on avian flu from NatureNature (journal)Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...
- Nature Reports: Homepage: Avian Flu
- Pandemic Influenza: Domestic Preparedness Efforts Congressional Research Service Report on Pandemic Preparedness.
- A guide to bird flu and its symptoms from BBCBBCThe British Broadcasting Corporation is a British public service broadcaster. Its headquarters is at Broadcasting House in the City of Westminster, London. It is the largest broadcaster in the world, with about 23,000 staff...
Health - A Variety of Avian Flu Images and Pictures "Highly pathogenic avian influenza virus is on every top ten list available for potential agricultural bioweapon agents"
- 'The Threat of Bird Flu': HealthPolitics.com
- Is a Global Flu Pandemic Imminent? from Infection Control Today.
- Bird Flu is a Real Pandemic Threat to Humans by Leonard Crane, author of Ninth Day of Creation.
- Links to Bird Flu pictures (Hardin MD/Univ of Iowa)
External links
- Influenza Research Database – Database of influenza genomic sequences and related information.
- Health-EU portal EU response to influenza