Rhinovirus

Rhinoviruses (from the Greek (gen.) "nose") are the most common viral infectious agents in humans and are the predominant cause of the common cold. Rhinovirus infection proliferates in temperatures between 33â€"35 °C (91â€"95 °F), the temperatures found in the nose. Rhinoviruses consist of three species in the genus Enterovirus of the Picornaviridae family of viruses.

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 30 nanometers. By comparison, other viruses such as smallpox and vaccinia 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 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 autumn and winter, with most infections occurring between September to April. The seasonality may be due to the start of the school year and to people spending more time indoors (thus in proximity with each other), thereby increasing the chance of transmission of the virus. Lower ambient, especially outdoor, temperatures may also be factor given that rhinoviruses preferentially replicate at 32°C (89°F) as opposed to 37°C (98°F) - see following section.

Pathogenesis

The primary route of entry for human rhinoviruses is the upper respiratory tract (mouth and nose). Afterward, 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). Cell lysis occurs at the upper respiratory epithelium.

Infection occurs rapidly, with the virus adhering to surface receptors within 15 minutes of entering the respiratory tract. High risk individuals includes children and the elderly. Just over 50% of 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, at the other extreme, 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 where respiratory airflow is in continual contact to the (colder) extrasomatic environment.

Taxonomy

Rhinovirus was formerly a genus from the family Picornaviridae. The 39th Executive Committee (EC39) of the International Committee on Taxonomy of Viruses (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 Enterovirus 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 Enterovirus, family Picornaviridae.

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.

Structure

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 3' end. This is the same for all picornaviruses. 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 the 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.

Novel antiviral drugs

Interferon-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.

Vaccine

There are no vaccines against these viruses as there is little-to-no cross-protection between serotypes. At least 99 serotypes of Human rhinoviruses affecting humans have been sequenced. However, a study of the VP4 protein has shown it to be highly conserved among many serotypes of Human rhinovirus, opening up the potential for a future pan-serotype Human rhinovirus vaccine.

Prevention

Human rhinovirus is extremely contagious during the cold months of each year. The virus can live up to 3 hours outside human contact. Once contracted, a person is most contagious within the first 3 days. It is important to wash hands thoroughly with a reliable antimicrobial agent on a regular basis. Avoid touching the mouth or nose, as those are the most common portals of entry for the virus.

References

• Smith TJ, Chase ES, Schmidt TJ, Olson NH, Baker TS; Chase; Schmidt; Olson; Baker (1996). "Neutralizing antibody to Human rhinovirus 14 penetrates the receptor-binding canyon". Nature 383 (6598): 350â€"4. Bibcode:1996Natur.383..350S. doi:10.1038/383350a0. PMID 8848050. 

• Abraham G, Colonno RJ; Colonno (1984). "Many Human rhinovirus serotypes share the same cellular receptor". J. Virol. 51 (2): 340â€"5. PMC 254443. PMID 6086949. 

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)

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