Rhinovirus
Encyclopedia
Human rhinoviruses are the most common viral infective agents in humans and are the predominant cause of the common cold
. Rhinovirus infection proliferates in temperatures between 33–35 °C (91–95 °F), and this may be why it occurs primarily in the nose. Rhinovirus is a species in the genus Enterovirus
of the Picornaviridae family of virus
es.
There are 99 recognized types of Human rhinoviruses that differ according to their surface proteins. They are lytic
in nature and are among the smallest viruses, with diameters of about only 30 nanometers. Other viruses such as smallpox
and vaccinia
are around 10 times larger at about 300 nanometers.
Human rhinoviruses occur worldwide and are the primary cause of common cold
s. Symptom
s include sore throat
, runny nose
, nasal congestion
, sneezing
and cough
; sometimes accompanied by muscle aches
, fatigue, malaise
, headache
, muscle weakness
, or loss of appetite
. Fever
and extreme exhaustion are more usual in influenza
. Children may have six to twelve colds a year. In the United States, the incidence of colds is higher in the autumn and winter, with most infections occurring between September to April. The seasonality may be due to the start of the school year, or due to people spending more time indoors (thus in closer proximity with each other), increasing the chance of transmission of the virus.
. Afterward, the virus binds to ICAM-1
(Inter-Cellular Adhesion Molecule 1) also known as CD54 (Cluster of Differentiation 54) receptor
s on respiratory epithelial cells. As the virus replicates and spreads, infected cells release distress signals known as chemokine
s and cytokine
s (which in turn activate inflammatory mediators).
Infection occurs rapidly, with the virus adhering to surface receptors within 15 minutes of entering the respiratory tract. Just over 50% of symptomatic individuals will experience symptoms within 2 days of infection. Only about 5% of cases will have an incubation period
of less than 20 hours, and, on the other end, it is expected that 5% of cases would have an incubation period
of greater than four and a half days.
Human rhinoviruses preferentially grow at 32°C (89°F) as opposed to 37°C (98°F), hence infect the upper respiratory tract
.
(ICTV) met in Canada during June 2007 with new taxonomic proposals. In April 2008, the International Committee on Taxonomy of Viruses voted and ratified the following changes:
In July 2009, the ICTV voted and ratified a proposal to add a third species, Human rhinovirus C to the genus Enterovirus.
There have been a total of 215 taxonomic proposals, which have been approved and ratified since the 8th ICTV
Report of 2005.
Rhinovirus C, unlike the A and B species, may be able to cause severe infections.
genomes of between 7.2 and 8.5 kb
in length. At the 5' end of the genome
is a virus-encoded protein, and like mammalian mRNA, there is a 3' poly-A tail. Structural proteins are encoded in the 5' region of the genome and non structural at the 3' end. This is the same for all picornavirus
es. The viral particles themselves are not enveloped
and are icosahedral in structure.
The viral proteins are transcribed as a single, long polypeptide, which is cleaved into the structural and nonstructural viral proteins.
Human rhinoviruses are composed of a capsid
, that contains four viral proteins VP1, VP2, VP3 and VP4. VP1, VP2, and VP3 form the major part of the protein capsid. The much smaller VP4 protein has a more extended structure, and lies at interface between the capsid and the RNA genome. There are 60 copies of each of these proteins assembled as an icosahedron
. Antibodies are a major defense against infection with the epitopes lying on the exterior regions of VP1-VP3.
-alpha used intranasally was shown to be effective against Human rhinovirus infections. However, volunteers treated with this drug experienced some side effects, such as nasal bleeding, and began developing resistance to the drug. Subsequently, research into the treatment was abandoned.
Pleconaril is an orally bioavailable antiviral drug
being developed for the treatment of infections caused by picornaviruses. This drug acts by binding to a hydrophobic pocket in VP1, and stabilizes the protein capsid to such an extent that the virus cannot release its RNA genome into the target cell. When tested in volunteers, during the clinical trials, this drug caused a significant decrease in mucus
secretions and illness-associated symptoms. Pleconaril is not currently available for treatment of Human rhinoviral infections, as its efficacy in treating these infections is under further evaluation.
There are potentially other substances such as Iota-Carrageenan that may lead to the creation of drugs to combat the Human rhinovirus.
In Asthma: Human rhinoviruses have been recently associated with the majority of asthma exacerbations for which current therapy is inadequate. Intercellular adhesion molecule 1 (ICAM-1) has a central role in airway inflammation in asthma, and it is the receptor for 90% of Human rhinoviruses. Human rhinovirus infection of airway epithelium induces ICAM-1. Desloratadine and loratadine are compounds belonging to the new class of H1-receptor blockers. Anti-inflammatory properties of antihistamines have been recently documented, although the underlying molecular mechanisms are not completely defined. These effects are unlikely to be mediated by H1-receptor antagonism and suggest a novel mechanism of action that may be important for the therapeutic control of virus-induced asthma exacerbations.
s. At least 99 serotypes of Human rhinoviruses affecting humans have been sequenced
.
However, recent study of the VP4 protein has shown it to be highly conserved amongst many serotypes of Human rhinovirus, opening up the potential for a future pan-serotype Human rhinovirus vaccine.
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
. Rhinovirus infection proliferates in temperatures between 33–35 °C (91–95 °F), and this may be why it occurs primarily in the nose. Rhinovirus is a species in the genus Enterovirus
Enterovirus
Enteroviruses are a genus of ssRNA viruses associated with several human and mammalian diseases. Serologic studies have distinguished 66 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the...
of the Picornaviridae 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.
There are 99 recognized types of Human rhinoviruses that differ according to their surface proteins. They are lytic
Lytic cycle
The lytic cycle is one of the two cycles of viral reproduction, the other being the lysogenic cycle. The lytic cycle is typically considered the main method of viral replication, since it results in the destruction of the infected cell...
in nature and are among the smallest viruses, with diameters of about only 30 nanometers. Other viruses such as smallpox
Smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...
and vaccinia
Vaccinia
Vaccinia virus is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, and which encodes for approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a mass of...
are around 10 times larger at about 300 nanometers.
Transmission and epidemiology
There are two modes of transmission: via aerosols of respiratory droplets and from contaminated surfaces, including direct person-to-person contact.Human rhinoviruses occur worldwide and are the primary cause of common cold
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
s. Symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s include sore throat
Pharyngitis
Pharyngitis is an inflammation of the throat or pharynx. In most cases it is quite painful, and is the most common cause of a sore throat.Like many types of inflammation, pharyngitis can be acute – characterized by a rapid onset and typically a relatively short course – or chronic....
, runny nose
Rhinitis
Rhinitis , commonly known as a stuffy nose, is the medical term describing irritation and inflammation of some internal areas of the nose. The primary symptom of rhinitis is nasal dripping. It is caused by chronic or acute inflammation of the mucous membrane of the nose due to viruses, bacteria or...
, nasal congestion
Nasal congestion
Nasal congestion is the blockage of the nasal passages usually due to membranes lining the nose becoming swollen from inflamed blood vessels. It is also known as nasal blockage, nasal obstruction, blocked nose, stuffy nose, or stuffed up nose.Nasal congestion has many causes and can range from a...
, sneezing
Sneeze
A sneeze is a semi-autonomous, convulsive expulsion of air from the lungs through the nose and mouth, usually caused by foreign particles irritating the nasal mucosa...
and 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...
; sometimes accompanied by 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...
, fatigue, malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, muscle weakness
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
, or loss of appetite
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
. 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...
and extreme exhaustion are more usual in influenza
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...
. Children may have six to twelve colds a year. In the United States, the incidence of colds is higher in the autumn and winter, with most infections occurring between September to April. The seasonality may be due to the start of the school year, or due to people spending more time indoors (thus in closer proximity with each other), increasing the chance of transmission of the virus.
Pathogenesis
The primary route of entry for Human rhinoviruses is the upper respiratory tractRespiratory tract
In humans the respiratory tract is the part of the anatomy involved with the process of respiration.The respiratory tract is divided into 3 segments:*Upper respiratory tract: nose and nasal passages, paranasal sinuses, and throat or pharynx...
. Afterward, the virus binds to ICAM-1
ICAM-1
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system...
(Inter-Cellular Adhesion Molecule 1) also known as CD54 (Cluster of Differentiation 54) receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s on respiratory epithelial cells. As the virus replicates and spreads, infected cells release distress signals known as chemokine
Chemokine
Chemokines are a family of small cytokines, or proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines...
s and cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s (which in turn activate inflammatory mediators).
Infection occurs rapidly, with the virus adhering to surface receptors within 15 minutes of entering the respiratory tract. Just over 50% of symptomatic individuals will experience symptoms within 2 days of infection. Only about 5% of cases will have an incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...
of less than 20 hours, and, on the other end, it is expected that 5% of cases would have an incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...
of greater than four and a half days.
Human rhinoviruses preferentially grow at 32°C (89°F) as opposed to 37°C (98°F), hence infect the upper respiratory tract
Upper respiratory tract
The upper respiratory tract or upper airway primarily refers to the parts of the respiratory system lying outside of the thorax or above the sternal angle. Another definition commomly used in medicine is the airway above the glottis or vocal cords...
.
Taxonomy
Rhinovirus was formerly a genus from the family Picornaviridae. The 39th Executive Committee (EC39) of the International Committee on Taxonomy of VirusesInternational Committee on Taxonomy of Viruses
The International Committee on Taxonomy of Viruses is a committee which authorizes and organizes the taxonomic classification of viruses. They have developed a universal taxonomic scheme for viruses and aim to describe all the viruses of living organisms. Members of the committee are considered to...
(ICTV) met in Canada during June 2007 with new taxonomic proposals. In April 2008, the International Committee on Taxonomy of Viruses voted and ratified the following changes:
- 2005.264V.04 To remove the following species from the existing genus Rhinovirus in the family Picornaviridae:
- Human rhinovirus A
- Human rhinovirus B
- 2005.265V.04 To assign the following species to the genus EnterovirusEnterovirusEnteroviruses are a genus of ssRNA viruses associated with several human and mammalian diseases. Serologic studies have distinguished 66 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the...
in the family Picornaviridae:- Human rhinovirus A
- Human rhinovirus B
- 2005.266V.04 To remove the existing genus Rhinovirus from the family Picornaviridae. Note: The genus Rhinovirus hereby disappears.
In July 2009, the ICTV voted and ratified a proposal to add a third species, Human rhinovirus C to the genus Enterovirus.
- 2008.084V.A.HRV-C-Sp 2008.084V To create a new species named Human rhinovirus C in the genus EnterovirusEnterovirusEnteroviruses are a genus of ssRNA viruses associated with several human and mammalian diseases. Serologic studies have distinguished 66 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the...
, family Picornaviridae.
There have been a total of 215 taxonomic proposals, which have been approved and ratified since the 8th ICTV
International Committee on Taxonomy of Viruses
The International Committee on Taxonomy of Viruses is a committee which authorizes and organizes the taxonomic classification of viruses. They have developed a universal taxonomic scheme for viruses and aim to describe all the viruses of living organisms. Members of the committee are considered to...
Report of 2005.
Rhinovirus C, unlike the A and B species, may be able to cause severe infections.
Structure
Rhinoviruses have single-stranded positive sense RNARNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
genomes of between 7.2 and 8.5 kb
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
in length. At the 5' end of 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....
is a virus-encoded protein, and like mammalian mRNA, there is a 3' poly-A tail. Structural proteins are encoded in the 5' region of the genome and non structural at the 3' end. This is the same for all picornavirus
Picornavirus
A picornavirus is a virus belonging to the family Picornaviridae. Picornaviruses are non-enveloped, positive-stranded RNA viruses with an icosahedral capsid. The genome RNA is unusual because it has a protein on the 5' end that is used as a primer for transcription by RNA polymerase...
es. The viral particles themselves are not enveloped
Viral envelope
Many viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...
and are icosahedral in structure.
The viral proteins are transcribed as a single, long polypeptide, which is cleaved into the structural and nonstructural viral proteins.
Human rhinoviruses are composed of a capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
, that contains four viral proteins VP1, VP2, VP3 and VP4. VP1, VP2, and VP3 form the major part of the protein capsid. The much smaller VP4 protein has a more extended structure, and lies at interface between the capsid and the RNA genome. There are 60 copies of each of these proteins assembled as an icosahedron
Icosahedron
In geometry, an icosahedron is a regular polyhedron with 20 identical equilateral triangular faces, 30 edges and 12 vertices. It is one of the five Platonic solids....
. Antibodies are a major defense against infection with the epitopes lying on the exterior regions of VP1-VP3.
Novel antiviral drugs
InterferonInterferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
-alpha used intranasally was shown to be effective against Human rhinovirus infections. However, volunteers treated with this drug experienced some side effects, such as nasal bleeding, and began developing resistance to the drug. Subsequently, research into the treatment was abandoned.
Pleconaril is an orally bioavailable antiviral drug
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
being developed for the treatment of infections caused by picornaviruses. This drug acts by binding to a hydrophobic pocket in VP1, and stabilizes the protein capsid to such an extent that the virus cannot release its RNA genome into the target cell. When tested in volunteers, during the clinical trials, this drug caused a significant decrease in mucus
Mucus
In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...
secretions and illness-associated symptoms. Pleconaril is not currently available for treatment of Human rhinoviral infections, as its efficacy in treating these infections is under further evaluation.
There are potentially other substances such as Iota-Carrageenan that may lead to the creation of drugs to combat the Human rhinovirus.
In Asthma: Human rhinoviruses have been recently associated with the majority of asthma exacerbations for which current therapy is inadequate. Intercellular adhesion molecule 1 (ICAM-1) has a central role in airway inflammation in asthma, and it is the receptor for 90% of Human rhinoviruses. Human rhinovirus infection of airway epithelium induces ICAM-1. Desloratadine and loratadine are compounds belonging to the new class of H1-receptor blockers. Anti-inflammatory properties of antihistamines have been recently documented, although the underlying molecular mechanisms are not completely defined. These effects are unlikely to be mediated by H1-receptor antagonism and suggest a novel mechanism of action that may be important for the therapeutic control of virus-induced asthma exacerbations.
Vaccine
There are no vaccines against these viruses as there is little-to-no cross-protection between serotypeSerotype
Serotype or serovar refers to distinct variations within a subspecies of bacteria or viruses. These microorganisms, viruses, or cells are classified together based on their cell surface antigens...
s. At least 99 serotypes of Human rhinoviruses affecting humans have been sequenced
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
.
However, recent study of the VP4 protein has shown it to be highly conserved amongst many serotypes of Human rhinovirus, opening up the potential for a future pan-serotype Human rhinovirus vaccine.
External links
- VIDEO: Rhinoviruses, the Old, the New and the UW James E. Gern, MD, speaks at the University of Wisconsin School of Medicine and Public Health, 2008.
- How Big is a Human rhinovirus? (animation)