Flavivirus
Encyclopedia
Flavivirus is a genus of the family Flaviviridae
. This genus includes the West Nile virus
, dengue virus
, tick-borne encephalitis virus
, yellow fever virus
, and several other virus
es which may cause encephalitis
.
Flaviviruses are named from the yellow fever virus, the type virus for the family; flavus means yellow in Latin
. Yellow fever in turn was named because of its propensity to cause yellow jaundice
in victims.
Flaviviruses share a common size (40-65 nm), symmetry (enveloped, icosahedral nucleocapsid), nucleic acid
(positive-sense, single stranded RNA
approximately 10,000–11,000 bases), and appearance in the electron microscope
.
These viruses are transmitted by the bite from an infected arthropod (mosquito or tick). Human infections with these viruses are typically incidental, as humans are unable to replicate the virus to high enough titres to reinfect arthropod
s and thus continue the virus life cycle. The exceptions to this are yellow fever and dengue viruses, which still require mosquito vectors, but are well-enough adapted to humans as to not necessarily depend upon animal hosts (although both continue have important animal transmission routes as well).
Other virus transmission routes include handling infected animal carcasses, blood transfusion, child birth and through consumption of unpasteurised milk products. The transmission from animals to humans without an intermediate vector arthropod is thought to be unlikely. For example, early tests with yellow fever showed that the disease is not contagious
.
of the host cells. The genome
mimics the cellular mRNA molecule in all aspects except for the absence of the poly-adenylated (poly-A) tail. This feature allows the virus to exploit cellular apparatus to synthesise both structural and non-structural proteins, during replication. The cellular ribosome
is crucial to the replication of the flavivirus, as it translates the RNA, in a similar fashion to cellular mRNA, resulting in the synthesis of a single polyprotein. In general the genome encodes 3 structural proteins (Capsid, prM, and Envelope) and 8 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, 2K, NS4B and NS5). The genomic RNA is modified at the 5′ end of positive strand genomic RNA with a cap 1 structure (me7-GpppA-me2)
Cellular RNA cap structures are formed via the action of an RNA triphosphatase, guanylyltransferase, N7-methyltransferase and 2′-O methyltransferase. The virus encodes these activities in its non structural proteins. The NS3 protein encodes a RNA triphosphatase
within its helicase domain. It uses the helicase ATP hydrolysis site to remove the γ-phosphate from the 5′ end of the RNA. The N-terminal domain of the non structural protein 5 (NS5) has both the N7-methyltransferase
and guanylyltransferase activities necessary for forming mature RNA cap structures. RNA binding affinity is reduced by the presence of ATP
or GTP
and enhanced by S-adenosyl methionine
. This protein also encodes an 2′-O methyltransferase.
Once translated
, the polyprotein is cleaved by a combination of viral and host proteases to release mature polypeptide products. Nevertheless, cellular post-translational modification is dependent on the presence of a poly-A tail; therefore this process is not host-dependent. Instead, the polyprotein contains an autocatalytic feature which automatically releases the first peptide, a virus specific enzyme. This enzyme is then able to cleave
the remaining polyprotein into the individual products. One of the products cleaved is a polymerase
, responsible for the synthesis of a (-) sense RNA molecule. Consequently this molecule acts as the template for the synthesis of the genomic progeny
RNA.
Flavivirus genomic RNA replication occurs on rough endoplasmic reticulum membranes in membranous compartments.
New viral particles are subsequently assembled. This occurs during the budding
process which is also responsible for the accumulation of the envelope and cell lysis
.
s which are conserved and restricted to the flavivirus family. The majority of analysis has been carried out using West Nile virus
(WNV) to study the function the 3'UTR.
Currently 8 secondary structures have been identified within the 3'UTR of WNV and are (in the order in which they are found with the 3'UTR) SL-I, SL-II, SL-III, SL-IV, DB1, DB2 and CRE. Some of these secondary structres have been characterised and are important in facilitating viral replication
and protecting the 3'UTR from 5' endonuclease
digestion. Nuclease resistance protects the downstream 3' UTR RNA fragment from degradation and is essential for virus-induced cytopathicity and pathogenicity.
SL-II has been suggested to contribute to nuclease resistance. It may be related to another hairpin loop identified in the 5'UTR of the Japanese encephalitis virus (JEV) genome. The JEV hairpin is significantly over-represented upon host cell infection and it has been suggested that the hairpin structure may play a role in regulating RNA synthesis.
This secondary structure is located within the 3'UTR of the genome of Flavivirus upstream of the DB elements. The function of this conserved structure is unknown but is thought to contribute to ribonuclease resistance.
These two conserved secondary structures are also known as pseudo-repeat elements. They were originally identified within the genome of Dengue virus
and are found adjacent to each other within the 3'UTR. They appear to be widely conserved across the Flaviviradae. These DB elements have a secondary structure consisting of three helices and they play a role in ensuring efficient translation. Deletion of DB1 has a small but significant reduction in translation but deletion of DB2 has little effect. Deleting both DB1 and DB2 reduced translation efficiency of the viral genome to 25%.
CRE is the Cis-acting replication element, also known as the 3'SL RNA elements, and is thought to be essential in viral replication by facilitating the formation of a "replication complex". Although evidence has been presented for an existence of a pseudoknot
structure in this RNA, it does not appear to be well conserved across flaviviruses. Deletions of the 3' UTR of flaviviruses have been shown to be lethal for infectious clones.
A conserved hairpin (cHP)
structure was later found in several Flavivirus genome
s and is thought to direct translation of capsid proteins.
Flaviviridae
The Flaviviridae are a family of viruses that are primarily spread through arthropod vectors . The family gets its name from Yellow Fever virus, a type virus of Flaviviridae; flavus means yellow in Latin...
. This genus includes the West Nile virus
West Nile virus
West Nile virus is a virus of the family Flaviviridae. Part of the Japanese encephalitis antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, domestic...
, dengue virus
Dengue virus
Dengue virus in one of four serotypes is the cause of dengue fever. It is a mosquito-borne single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus...
, tick-borne encephalitis virus
Tick-borne meningoencephalitis
Tick-borne encephalitis is a viral infectious disease involving the central nervous system. The disease most often manifests as meningitis, encephalitis, or meningoencephalitis. Although TBE is most commonly recognized as a neurological disorder, mild fever can also occur...
, yellow fever virus
Yellow fever
Yellow fever is an acute viral hemorrhagic disease. The virus is a 40 to 50 nm enveloped RNA virus with positive sense of the Flaviviridae family....
, and several other 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 which may cause encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
.
Flaviviruses are named from the yellow fever virus, the type virus for the family; flavus means yellow in Latin
Latin
Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...
. Yellow fever in turn was named because of its propensity to cause yellow jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
in victims.
Flaviviruses share a common size (40-65 nm), symmetry (enveloped, icosahedral nucleocapsid), nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
(positive-sense, single stranded RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
approximately 10,000–11,000 bases), and appearance in the electron microscope
Electron microscope
An electron microscope is a type of microscope that uses a beam of electrons to illuminate the specimen and produce a magnified image. Electron microscopes have a greater resolving power than a light-powered optical microscope, because electrons have wavelengths about 100,000 times shorter than...
.
These viruses are transmitted by the bite from an infected arthropod (mosquito or tick). Human infections with these viruses are typically incidental, as humans are unable to replicate the virus to high enough titres to reinfect arthropod
Arthropod
An arthropod is an invertebrate animal having an exoskeleton , a segmented body, and jointed appendages. Arthropods are members of the phylum Arthropoda , and include the insects, arachnids, crustaceans, and others...
s and thus continue the virus life cycle. The exceptions to this are yellow fever and dengue viruses, which still require mosquito vectors, but are well-enough adapted to humans as to not necessarily depend upon animal hosts (although both continue have important animal transmission routes as well).
Other virus transmission routes include handling infected animal carcasses, blood transfusion, child birth and through consumption of unpasteurised milk products. The transmission from animals to humans without an intermediate vector arthropod is thought to be unlikely. For example, early tests with yellow fever showed that the disease is not contagious
Contagious disease
A contagious disease is a subset category of infectious diseases , which are easily transmitted by physical contact with the person suffering the disease, or by their secretions or objects touched by them....
.
Replication
Flaviviruses have a (+) sense RNA genome and replicate in the cytoplasmCytoplasm
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...
of the host cells. The genome
Genome
In 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....
mimics the cellular mRNA molecule in all aspects except for the absence of the poly-adenylated (poly-A) tail. This feature allows the virus to exploit cellular apparatus to synthesise both structural and non-structural proteins, during replication. The cellular 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....
is crucial to the replication of the flavivirus, as it translates the RNA, in a similar fashion to cellular mRNA, resulting in the synthesis of a single polyprotein. In general the genome encodes 3 structural proteins (Capsid, prM, and Envelope) and 8 non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, 2K, NS4B and NS5). The genomic RNA is modified at the 5′ end of positive strand genomic RNA with a cap 1 structure (me7-GpppA-me2)
Cellular RNA cap structures are formed via the action of an RNA triphosphatase, guanylyltransferase, N7-methyltransferase and 2′-O methyltransferase. The virus encodes these activities in its non structural proteins. The NS3 protein encodes a RNA triphosphatase
RNA triphosphatase
-RNA Triphosphatase :RNA 5'Triphosphatase includes the phosphatases that cleave the γ-βphosphoanhydride bond of nascent mRNA molecule and releases the free phosphate group...
within its helicase domain. It uses the helicase ATP hydrolysis site to remove the γ-phosphate from the 5′ end of the RNA. The N-terminal domain of the non structural protein 5 (NS5) has both the N7-methyltransferase
Methyltransferase
A methyltransferase is a type of transferase enzyme that transfers a methyl group from a donor to an acceptor.Methylation often occurs on nucleic bases in DNA or amino acids in protein structures...
and guanylyltransferase activities necessary for forming mature RNA cap structures. RNA binding affinity is reduced by the presence of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
or GTP
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
and enhanced by S-adenosyl methionine
S-Adenosyl methionine
S-Adenosyl methionine is a common cosubstrate involved in methyl group transfers. SAM was first discovered in Italy by G. L. Cantoni in 1952. It is made from adenosine triphosphate and methionine by methionine adenosyltransferase . Transmethylation, transsulfuration, and aminopropylation are the...
. This protein also encodes an 2′-O methyltransferase.
Once translated
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
, the polyprotein is cleaved by a combination of viral and host proteases to release mature polypeptide products. Nevertheless, cellular post-translational modification is dependent on the presence of a poly-A tail; therefore this process is not host-dependent. Instead, the polyprotein contains an autocatalytic feature which automatically releases the first peptide, a virus specific enzyme. This enzyme is then able to cleave
Bond cleavage
Bond cleavage, or scission, is the splitting of chemical bonds.If the two electrons in a cleaved covalent bond are divided between the products, the process is known as homolytic fission and free redicals are generated by homolytic cleavage the process is known as homolytic fission or homolysis...
the remaining polyprotein into the individual products. One of the products cleaved is a polymerase
Polymerase
A polymerase is an enzyme whose central function is associated with polymers of nucleic acids such as RNA and DNA.The primary function of a polymerase is the polymerization of new DNA or RNA against an existing DNA or RNA template in the processes of replication and transcription...
, responsible for the synthesis of a (-) sense RNA molecule. Consequently this molecule acts as the template for the synthesis of the genomic progeny
Offspring
In biology, offspring is the product of reproduction, of a new organism produced by one or more parents.Collective offspring may be known as a brood or progeny in a more general way...
RNA.
Flavivirus genomic RNA replication occurs on rough endoplasmic reticulum membranes in membranous compartments.
New viral particles are subsequently assembled. This occurs during the budding
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...
process which is also responsible for the accumulation of the envelope and cell lysis
Lysis
Lysis refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate"....
.
RNA secondary structure elements
The (+) sense RNA genome of Flavivirus contains 5' and 3'untranslated regions (UTRs). The 3'UTRs are typically 0.3-0.5kb in length and contain a number of highly conserved secondary structureSecondary structure
In biochemistry and structural biology, secondary structure is the general three-dimensional form of local segments of biopolymers such as proteins and nucleic acids...
s which are conserved and restricted to the flavivirus family. The majority of analysis has been carried out using West Nile virus
West Nile virus
West Nile virus is a virus of the family Flaviviridae. Part of the Japanese encephalitis antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, domestic...
(WNV) to study the function the 3'UTR.
Currently 8 secondary structures have been identified within the 3'UTR of WNV and are (in the order in which they are found with the 3'UTR) SL-I, SL-II, SL-III, SL-IV, DB1, DB2 and CRE. Some of these secondary structres have been characterised and are important in facilitating viral replication
Viral replication
Viral replication is the term used by virologists to describe the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. From the perspective of the virus, the purpose of viral replication is...
and protecting the 3'UTR from 5' endonuclease
Endonuclease
Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain, in contrast to exonucleases, which cleave phosphodiester bonds at the end of a polynucleotide chain. Typically, a restriction site will be a palindromic sequence four to six nucleotides long. Most...
digestion. Nuclease resistance protects the downstream 3' UTR RNA fragment from degradation and is essential for virus-induced cytopathicity and pathogenicity.
- SL-II
SL-II has been suggested to contribute to nuclease resistance. It may be related to another hairpin loop identified in the 5'UTR of the Japanese encephalitis virus (JEV) genome. The JEV hairpin is significantly over-represented upon host cell infection and it has been suggested that the hairpin structure may play a role in regulating RNA synthesis.
- SL-IV
This secondary structure is located within the 3'UTR of the genome of Flavivirus upstream of the DB elements. The function of this conserved structure is unknown but is thought to contribute to ribonuclease resistance.
- DB1/DB2
These two conserved secondary structures are also known as pseudo-repeat elements. They were originally identified within the genome of Dengue virus
Dengue virus
Dengue virus in one of four serotypes is the cause of dengue fever. It is a mosquito-borne single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus...
and are found adjacent to each other within the 3'UTR. They appear to be widely conserved across the Flaviviradae. These DB elements have a secondary structure consisting of three helices and they play a role in ensuring efficient translation. Deletion of DB1 has a small but significant reduction in translation but deletion of DB2 has little effect. Deleting both DB1 and DB2 reduced translation efficiency of the viral genome to 25%.
- CRE
CRE is the Cis-acting replication element, also known as the 3'SL RNA elements, and is thought to be essential in viral replication by facilitating the formation of a "replication complex". Although evidence has been presented for an existence of 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...
structure in this RNA, it does not appear to be well conserved across flaviviruses. Deletions of the 3' UTR of flaviviruses have been shown to be lethal for infectious clones.
- cHP
A conserved hairpin (cHP)
Flavivirus capsid hairpin cHP
The Flavivirus capsid hairpin cHP is a conserved RNA hairpin structure identified within the capsid coding region of several flavivirus genomes. These positive strand RNA genomes are translated as a single polypeptide and subsequently cleaved into constituent proteins, the first of which is the...
structure was later found in several Flavivirus genome
Genome
In 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....
s and is thought to direct translation of capsid proteins.
Species
- Genus Flavivirus
- TickTickTicks are small arachnids in the order Ixodida, along with mites, constitute the subclass Acarina. Ticks are ectoparasites , living by hematophagy on the blood of mammals, birds, and sometimes reptiles and amphibians...
-borne viruses- MammalMammalMammals 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...
ian tick-borne virus group- Alkhurma virusAlkhurma virusAlkhurma virus is a member of the Flaviviridae virus family .-Virology:The virus has a positive sense single stranded RNA genome and replicates in the cytoplasm of the infected host cell...
(ALKV) - Gadgets Gully virus (GGYV)
- Kadam virusKadam virusThe Kadam virus is a tick-borne Flavivirus. It was first isolated by the Uganda Virus Research Institute in Entebbe, Uganda....
(KADV) - Kyasanur Forest disease virus (KFDV)
- Langat virusLangat virusLangat virus is a virus of the genus Flavivirus. For the first time Langat virus was isolated in Malaysia and Thailand. This virus is close to Omsk hemorrhagic fever virus, Kyasanur forest disease virus, Alkhurma virus, Louping ill virus and the Tick-borne encephalitis virus.The Langat virus does...
(LGTV) - Louping ill virus (LIV)
- Omsk hemorrhagic fever virus (OHFV)
- Powassan virusPowassan virusThe Powassan virus is a tick-borne encephalitis virus related to the classic TBE flavivirus. This disease had its earliest origins in the town of Powassan, Ontario, found in a young boy who eventually died from it....
(POWV) - Royal Farm virus (RFV)
- Tick-borne encephalitis virusTick-borne encephalitis virusTick-borne encephalitis virus is the virus associated with Tick-borne encephalitis.The responsible virus, Tick-Borne Encephalitis Virus , is a member of the genus Flavivirus...
(TBEV)
- Alkhurma virus
- SeabirdSeabirdSeabirds are birds that have adapted to life within the marine environment. While seabirds vary greatly in lifestyle, behaviour and physiology, they often exhibit striking convergent evolution, as the same environmental problems and feeding niches have resulted in similar adaptations...
tick-borne virus group- Meaban virus (MEAV)
- Saumarez Reef virus (SREV)
- Tyuleniy virus (TYUV)
- Mammal
- MosquitoMosquitoMosquitoes are members of a family of nematocerid flies: the Culicidae . The word Mosquito is from the Spanish and Portuguese for little fly...
-borne viruses- Calbertado virus
- Aroa virus group
- Aroa virus (AROAV)
- Dengue virus group
- Dengue virusDengue virusDengue virus in one of four serotypes is the cause of dengue fever. It is a mosquito-borne single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus...
(DENV) - Kedougou virus (KEDV)
- Dengue virus
- Japanese encephalitis virus group
- Cacipacore virus (CPCV)
- Koutango virus (KOUV)
- Japanese encephalitis virus (JEV)
- Murray Valley encephalitis virusMurray Valley encephalitis virusMurray Valley encephalitis virus is a zoonotic flavivirus endemic to northern Australia and Papua New Guinea. It is the causal agent of Murray Valley encephalitis and in humans can cause permanent neurological disease or death...
(MVEV) - St. Louis encephalitis virusSt. Louis EncephalitisSt. Louis Encephalitis is a disease caused by the Culex mosquito borne St. Louis Encephalitis virus. St. Louis encephalitis virus is related to Japanese encephalitis virus and is a member of the Flaviviridae subgroup. This disease mainly affects the United States...
(SLEV) - Usutu virus (USUV)
- West Nile virusWest Nile virusWest Nile virus is a virus of the family Flaviviridae. Part of the Japanese encephalitis antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, domestic...
(WNV) - Yaounde virus (YAOV)
- Kokobera virus group
- Kokobera virus (KOKV)
- Ntaya virus group
- Bagaza virus (BAGV)
- Ilheus virus (ILHV)
- Israel turkey meningoencephalomyelitis virus (ITV)
- Ntaya virus (NTAV)
- Tembusu virus (TMUV)
- Spondweni virus group
- Zika virusZika virusZika virus is a member of the Flaviviridae virus family and the flavivirus genus. In humans, it causes a disease known as Zika fever. It is related to dengue, yellow fever, West Nile and Japanese encephalitis, viruses that are also members of the virus family Flaviviridae...
(ZIKV)
- Zika virus
- Yellow fever virus group
- Banzi virus (BANV)
- Bouboui virus (BOUV)
- Edge Hill virus (EHV)
- Jugra virus (JUGV)
- Saboya virus (SABV)
- Sepik virus (SEPV)
- Uganda S virus (UGSV)
- Wesselsbron virus (WESSV)
- Yellow fever virus (YFV)
- Viruses with no known arthropodArthropodAn arthropod is an invertebrate animal having an exoskeleton , a segmented body, and jointed appendages. Arthropods are members of the phylum Arthropoda , and include the insects, arachnids, crustaceans, and others...
vector- Entebbe virus group
- Entebbe bat virus (ENTV)
- Yokose virus (YOKV)
- Modoc virus group
- Apoi virus (APOIV)
- Cowbone Ridge virus (CRV)
- Jutiapa virus (JUTV)
- Modoc virus (MODV)
- Sal Vieja virus (SVV)
- San Perlita virus (SPV)
- Rio Bravo virus group
- Bukalasa bat virus (BBV)
- Carey Island virus (CIV)
- Dakar bat virus (DBV)
- Montana myotis leukoencephalitis virus (MMLV)
- Phnom Penh bat virus (PPBV)
- Rio Bravo virus (RBV)
- Entebbe virus group
- Tick
Vaccines
The successful yellow fever 17D vaccine, introduced in 1937, produced dramatic reductions in epidemic activity. Effective killed Japanese encephalitis and Tick-borne encephalitis vaccines were introduced in the middle of the 20th century. Unacceptable adverse events have prompted change from a mouse-brain killed Japanese encephalitis vaccine to safer and more effective second generation Japanese encephalitis vaccines. These may come into wide use to effectively prevent this severe disease in the huge populations of Asia - North, South and Southeast. The dengue viruses produce many millions of infections annually due to transmission by a successful global mosquito vector. As mosquito control has failed, several dengue vaccines are in varying stages of development. A tetravalent chimeric vaccine that splices structural genes of the four dengue viruses onto a 17D yellow fever backbone is in Phase III clinical testing.External links
- MicrobiologyBytes: Flaviviruses
- Novartis Institute for Tropical Diseases (NITD) - Dengue Fever research at the Novartis Institute for Tropical Diseases (NITD)
- Dengueinfo.org - Depository of dengue virus genomic sequence data
- Viralzone: Flavivirus
- Virus Pathogen Database and Analysis Resource (ViPR): Flaviviridae
- Rfam entry for Flavivirus 3'UTR stem loop IV
- Rfam entry for Flavivirus DB element
- Rfam entry for Flavivirus 3' UTR cis-acting replication element (CRE)
- Rfam entry for the Japanese encephalitis virus (JEV) hairpin structure