Rhinovirus: Difference between revisions
Added "human rhinovirus C", which was recently discovered. http://www.sciencemag.org/cgi/content/full/324/5923/55 |
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[[Pleconaril]] is an orally bioavailable [[antiviral]] drug being developed for the treatment of infections caused by [[picornaviruses]].<ref name=Pevear_1999>{{cite journal | author = Pevear D, Tull T, Seipel M, Groarke J | title = Activity of pleconaril against enteroviruses. | journal = Antimicrob Agents Chemother | volume = 43 | issue = 9 | pages = 2109–15 | year = 1999 | pmid = 10471549}}</ref> 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 rhinoviral infections, as its efficacy in treating these infections is under further evaluation.<ref name=Fleisher_2003>{{cite journal | author = Fleischer R, Laessig K | title = Safety and efficacy evaluation of pleconaril for treatment of the common cold. | journal = Clin Infect Dis | volume = 37 | issue = 12 | pages = 1722 | year = 2003 | pmid = 14689362 | doi = 10.1086/379830}}</ref> |
[[Pleconaril]] is an orally bioavailable [[antiviral]] drug being developed for the treatment of infections caused by [[picornaviruses]].<ref name=Pevear_1999>{{cite journal | author = Pevear D, Tull T, Seipel M, Groarke J | title = Activity of pleconaril against enteroviruses. | journal = Antimicrob Agents Chemother | volume = 43 | issue = 9 | pages = 2109–15 | year = 1999 | pmid = 10471549}}</ref> 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 rhinoviral infections, as its efficacy in treating these infections is under further evaluation.<ref name=Fleisher_2003>{{cite journal | author = Fleischer R, Laessig K | title = Safety and efficacy evaluation of pleconaril for treatment of the common cold. | journal = Clin Infect Dis | volume = 37 | issue = 12 | pages = 1722 | year = 2003 | pmid = 14689362 | doi = 10.1086/379830}}</ref> |
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There are potentially other substances such as Iota-Carrageenan that may lead to the creation of drugs to combat rhinovirus. <ref>[http://www.ncbi.nlm.nih.gov/pubmed/18817582?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_PMC&linkpos=2&log$=citedinpmcarticles&logdbfrom=pubmed]</ref> |
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==Vaccine== |
==Vaccine== |
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Revision as of 20:50, 23 June 2009
| Rhinovirus | |
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| Molecular surface of a rhinovirus, showing protein spikes | |
| Virus classification | |
| Group: | Group IV ((+)ssRNA)
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| Order: | |
| Family: | |
| Genus: | Rhinovirus
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Rhinovirus (from the Greek rhin- which means "nose") was a genus of the Picornaviridae family of viruses. It has been now merged into Enteroviruses.
Rhinoviruses are the most common viral infective agents in humans, and a causative agent of the common cold. It is lytic in nature.
Rhinoviruses have single-stranded positive sense RNA 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 end. This is the same for all picornaviruses. The viral particles themselves are not enveloped and are icosahedral in structure.
Rhinovirus also grows best in the temperatures between 33–35 °C, and this may be the reason which the reproduction occurs in the nose. It is sensitive to acidic environment.
The viral proteins are transcribed as a single, long polypeptide, which is cleaved into the structural and nonstructural viral proteins.[1]
Structure
Rhinoviruses are composed of a capsid, that contains four viral proteins VP1, VP2, VP3 and VP4.[2][3] 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.
Transmission and epidemiology
There are two modes of transmission: via aerosols of respiratory droplets and from contaminated surfaces, including direct person-to-person contact. A high majority of colds are transmitted by autoinoculation by contact with contaminated surfaces.
Rhinoviruses occur worldwide and are the primary cause of common colds. Symptoms 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 fall 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 rhinoviruses is the upper respiratory tract. Afterwards, the virus binds to ICAM-1 (Inter-Cellular Adhesion Molecule 1) also known as CD54 (Cluster of Differentiation 54) receptors on respiratory epithelial cells. As the virus replicates and spreads, infected cells release distress signals known as chemokines and cytokines (which in turn activate inflammatory mediators).
Infection occurs rapidly, with the virus adhering to surface receptors within 15 minutes of entering the respiratory tract. The incubation period is generally 8-10 hours before symptoms begin to occur.[4]
Rhinoviruses preferentially grow at 32 °C as opposed to 37 °C, hence infect the upper respiratory tract.
Novel antiviral drugs
Interferon-alpha used intranasally was shown to be effective against 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.[5] 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 rhinoviral infections, as its efficacy in treating these infections is under further evaluation.[6]
There are potentially other substances such as Iota-Carrageenan that may lead to the creation of drugs to combat rhinovirus. [7]
Vaccine
There are no vaccines against these viruses as there is little-to-no cross-protection between serotypes. At least 99 serotypes of rhinoviruses affecting humans have been sequenced.[8][9]
References
- ^ "Rhinoviruses:Replication", Encyclopedia of Life Sciences, John Wiley & Sons
- ^ Rossmann M, Arnold E, Erickson J, Frankenberger E, Griffith J, Hecht H, Johnson J, Kamer G, Luo M, Mosser A (1985). "Structure of a human common cold virus and functional relationship to other picornaviruses". Nature. 317 (6033): 145–53. doi:10.1038/317145a0. PMID 2993920.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Smith T, Kremer M, Luo M, Vriend G, Arnold E, Kamer G, Rossmann M, McKinlay M, Diana G, Otto M (1986). "The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating". Science. 233 (4770): 1286–93. doi:10.1126/science.3018924. PMID 3018924.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ McCoy, Lori. "Rhinovirus: An Unstoppable Cause of the Common Cold". The Science Creative Quarterly.
- ^ Pevear D, Tull T, Seipel M, Groarke J (1999). "Activity of pleconaril against enteroviruses". Antimicrob Agents Chemother. 43 (9): 2109–15. PMID 10471549.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Fleischer R, Laessig K (2003). "Safety and efficacy evaluation of pleconaril for treatment of the common cold". Clin Infect Dis. 37 (12): 1722. doi:10.1086/379830. PMID 14689362.
- ^ [1]
- ^ Mary Engel (February 13, 2009), "Rhinovirus strains' genomes decoded; cold cure-all is unlikely: The strains are probably too different for a single treatment or vaccine to apply to all varieties, scientists say", Los Angeles Times
- ^ Palmenberg, A. C. (2009), "Sequencing and Analyses of All Known Human Rhinovirus Genomes Reveals Structure and Evolution", Science, 324: 55, doi:10.1126/science.1165557, PMID 19213880
- Smith TJ, Chase ES, Schmidt TJ, Olson NH, Baker TS (1996). "Neutralizing antibody to human rhinovirus 14 penetrates the receptor-binding canyon". Nature. 383 (6598): 350–4. doi:10.1038/383350a0. PMID 8848050.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
- Abraham G, Colonno RJ (1984). "Many rhinovirus serotypes share the same cellular receptor". J. Virol. 51 (2): 340–5. PMC 254443. PMID 6086949.
External links
- VIDEO: Rhinoviruses, the Old, the New and the UWJames E. Gern, MD, speaks at the University of Wisconsin School of Medicine and Public Health, 2008.
- How Big is a Rhinovirus? (animation)