Human rhinovirus A (HRV-A)
Rhinovirus (from the Greek rhin-, which means "nose") is a genus of the Picornaviridae family of viruses. Rhinoviruses are the most common viral infective agents in humans, and a causative agent of the common cold. There are over 105 serologic virus types that cause cold symptoms, and rhinoviruses are responsible for approximately 50% of all cases.
Rhinoviruses have single-stranded positive sense RNA genomes of between 7.2 and 8.5kb 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.
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.
Transmission and epidemiology
There are two modes of transmission: via aerosols of respiratory droplets and from contaminated surfaces, including direct person-to-person contact.
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 ten colds a year (and up to 12 colds a year for school children). 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.
The primary route of entry for rhinoviruses is the upper respiratory tract. Afterwards, the virus binds to ICAM-1 (intracellular adhesion molecule -1) 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 .
Rhinoviruses rarely cause lower respiratory tract disease probably because they grow poorly at 37°C.
Interferon-alpha used intranasally was shown to be protective to rhinovirus infections. However, volunteers treated with this drug experienced some side effects, such as nasal bleeding, and resistance was also developing toward the drug. Hence, all research put into this drug was ceased.
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 rhinoviral infections, as its efficacy in treating these infections is under further evaluation.
- 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. PMID 2993920.
- 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. PMID 3018924.
- 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.
- Fleischer R, Laessig K (2003). "Safety and efficacy evaluation of pleconaril for treatment of the common cold". Clin Infect Dis. 37 (12): 1722. PMID 14689362.
- Heikkinen T, Järvinen A (2003). "The common cold". Lancet. 361 (9351): 51–9. doi:10.1016/S0140-6736(03)12162-9. PMID 12517470.
- Louie JK, Roy-Burman A, Guardia-Labar L, Boston EJ, Kiang D, Padilla T; et al. (2009). "Rhinovirus associated with severe lower respiratory tract infections in children". Pediatr Infect Dis J. 28 (4): 337–9. doi:10.1097/INF.0b013e31818ffc1b. PMID 19258921.
- Smith, T. J., Chase, E. S., Schmidt, T. J., Olson, N. H. & Baker, T. S. (1996). Neutralizing antibody to human rhinovirus 14 penetrates the receptor-binding canyon. Nature 383, 350-354.
- Abraham, G. & Colonno, R. J. (1984). Many rhinovirus serotypes share the same cellular receptor. J. Virol. 51: 340-345.