Human rhinovirus (HRV) infections cause 70% of virus‐related wheezing exacerbations and cold and flu‐like disease. They are associated with otitis media, sinusitis and pneumonia. Annually, the health and socioeconomic impact of HRV infections costs billions of dollars. Since 1987, 100 officially recognised HRV serotypes have resided in two genetically distinct species, HRV‐A and HRV‐B. Their genome sequences were deduced in 2009. Recently a new species, HRV‐C was recognised, containing 60 genotypes, of which only two have been isolated in primary tissue. Little is known about HRV‐Cs. The HRVs reside within the genus Enterovirus, family Picornaviridae. What drives the development and maintenance of so many distinct viruses is unknown. What role recombination plays in generating this diversity and whether there are species‐specific circulation patterns and clinical outcomes remains unclear. In short, much remains uncertain about the HRVs but the current key features and clinical outcomes from HRV infection are presented.

Key Concepts:

  • The nonenveloped HRVs have a small RNA genome of approximately 7000 base pairs.

  • A third, new species of HRV, HRV‐C was described in 2007; all species reside within the genus Enterovirus, family Picornaviridae.

  • HRV prevalence peaks twice per year.

  • HRVs cause cold and flu‐like symptoms and trigger asthma and chronic obstructive pulmonary disease exacerbations.

  • HRVs are associated with diseases such as otitis media, sinusitis and pneumonia.

  • HRV infections are associated with considerable direct and indirect healthcare expenditure annually.

Keywords: rhinovirus; molecular detection; virology; HRV; respiratory infections; common cold; asthma; rhinovirus epidemiology

Figure 1.

Schematic representations of an HRV genome and its components. The genome structure is illustrated to identify the polyprotein and the subsequent precursory (P1‐3) and matured proteins (named in filled boxes below the genome). The structural and nonstructural regions encompass 11 proteins. The regions commonly used for taxonomic placement are underlined by dashed bars. Each linear RNA genome of a rhinovirus contains approximately 7200 nucleotides. The RNA is polyadenylated at the 3′‐terminus and covalently bound to a small protein at the 5′‐terminus known as the virion protein, genome (VPg, encoded by 3B), which has a role in the initiation of RNA synthesis (Rueckert, ). The 5′UTR contains important secondary structures termed internal ribosome entry sites. Another secondary structure, the cis‐acting replication element (stem loop structure) is found in an HRV species‐specific location (labelled with A, B, C for the HRV species or human enterovirus).

Figure 2.

Comparison of predicted protomers. (a) A simplified depiction of two facing protomers on a viral capsid (shaded areas). As a guide for visualising loop length, a dashed and a dotted line are spaced equidistantly and represent proximal and distal positions from the virion core, respectively. (b) Ribbon depiction of two opposing viral protomers from HRV‐C3, HRV‐2 (minor group) and HRV‐14 (major group). HRV‐C3 (f.QPM) proteins were predicted by in silico matching to the empirically derived HRV‐16 and HRV‐14 structure. Protomers consist of one copy each of VP1, VP2, VP3 and VP4. β‐sheets are depicted as flat arrows and α‐helices as coiled ribbons. The formation of VP1‐VP3 into eight antiparallel β‐sheets is indicative of the ‘jellyroll’ conformation typical in picornaviruses. Major differences in the predicted HRV‐C3 VP1 include the shortened external loops between β‐sheets (*) and an additional C‐terminal sheet–loop–sheet formation (arrow indicates the same location on all protomers for comparison). Adapted from McErlean et al., with permission from Public Library of Science.

Figure 3.

Schematic diagram of cytoplasmic HRV attachment, uncoating, genome replication, translation, assembly and release. Genome replication occurs in association with membranes (not shown). Mature virions are released by cell lysis.

Figure 4.

A schematic representation of the human respiratory tract. The upper and lower respiratory tract (URT/LRT) and the components of the ear are indicated as are anatomical sites of interest. Beside the schematic are the approximate locations of URT and LRT diseases associated with infection by respiratory viruses. *Recurrent attacks of shortness of breath and wheezing due to spasmodic contraction of the bronchi attributed to infection. Adapted from Mackay et al., with permission from Caster Academic Press.



Andeweg AC, Bestebroer TM, Huybreghs M, Kimman TG and de Jong JC (1999) Improved detection of rhinoviruses in clinical samples by using a newly developed nested reverse transcription‐PCR assay. Journal of Clinical Microbiology 37: 524–530.

Andrewes CH (1966) Rhinoviruses and common colds. Annual Review of Medicine 17: 361–370.

Andries K, Dewindt B, Snoeks J et al. (1990) Two groups of rhinoviruses revealed by a panel of antiviral compounds present sequence divergence and differential pathogenicity. Journal of Virology 64: 1117–1123.

Arden KE, Faux CE, O'Neill NT et al. (2010) Molecular characterization and distinguishing features of a novel human rhinovirus (HRV) C, HRVC‐QCE, detected in children with fever, cough and wheeze during 2003. Journal of Clinical Virology 47: 219–223.

Arden KE and Mackay IM (2009) Human rhinoviruses: coming in from the cold. Genome Medicine 1: 44.

Arden KE and Mackay IM (2010) Newly identified human rhinoviruses: molecular methods heat up the cold viruses. Reviews in Medical Virology 20: 156–176.

Arden KE, McErlean P, Nissen MD, Sloots TP and Mackay IM (2006) Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections. Journal of Medical Virology 78: 1232–1240.

Arruda E, Pitkäranta A, Witek TJ, Doyle CA and Hayden FG (1997) Frequency and natural history of rhinovirus infections in adults during autumn. Journal of Clinical Microbiology 35: 2864–2868.

Behbehani AM and Lee LH (1964) Growth, plaque production and cationic stabilization of rhinovirus type 1 (Echovirus 28). Journal of Bacteriology 88: 1608–1611.

Bergamini G, Preiss T and Hentze MW (2000) Picornavirus IRESes and the poly(A) tail jointly promote cap‐independent translation in a mammalian cell‐free system. RNA 6: 1781–1790.

Bochkov YA, Palmenberg AC, Lee W‐M et al. (2011) Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C. Nature Medicine 17: 627–632.

Bryce J, Boschi‐Pinto C, Shibuya K and Black RE (2005) WHO estimates of the causes of death in children. Lancet 365: 1147–1152.

Buscho RF, Perkins JC, Knopf HLS, Kapikian AZ and Chanock RM (1972) Further characterization of the local respiratory tract antibody response induced by intranasal instillation of inactivated rhinovirus 13 vaccine. Journal of Immunology 108: 169–177.

Cate TR, Couch RB, Fleet WF et al. (1965) Production of tracheobronchitis in volunteers with rhinovirus in a small‐particle aerosol. American Journal of Epidemiology 81: 95–105.

Cate TR, Couch RB and Johnson KM (1964) Studies with rhinoviruses in volunteers: production of illness, effect of naturally acquired antibody, and demonstration of a protective effect not associated with serum antibody. Journal of Clinical Investigation 43: 56–67.

Cate TR, Rossen RD, Douglas RG Jr, Butler WT and Couch RB (1966) The role of nasal secretion and serum antibody in the rhinovirus common cold. American Journal of Epidemiology 84: 352–363.

Conant RM and Hamparian VV (1968) Rhinoviruses: basis for a numbering system. II Serologic characterization of prototype strains. Journal of Immunology 100: 107–113.

Cooney MK, Fox JP and Kenny GE (1982) Antigenic groupings of 90 rhinovirus serotypes. Infection and Immunity 37: 642–647.

Cooney MK and Kenny GE (1977) Demonstration of dual rhinovirus infection in humans by isolation of different serotypes in human heteroploid (HeLa) and human diploid fibroblast cell cultures. Journal of Clinical Microbiology 5: 202–207.

Cordey S, Gerlach D, Junier T et al. (2008) The cis‐acting replication elements define human enterovirus and rhinovirus species. RNA 14: 1568–1578.

Dick EC, Blumer CR and Evans AS (1967) Epidemiology of infections with rhinovirus types 43 and 55 in a group of University of Wisconsin student families. American Journal of Epidemiology 86: 386–400.

Douglas RG Jr, Cate TR, Gerone PJ and Couch RB (1966) Quantitative rhinovirus shedding patterns in volunteers. American Review of Respiratory Disease 94: 159–167.

Gern JE and Busse WW (2002) Relationship of viral infections to wheezing illnesses and asthma. Nature Reviews Immunology 2: 132–138.

Gern JE, Vrtis R, Grindle KA, Swenson C and Busse WW (2000) Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection. American Journal of Respiratory and Critical Care Medicine 162: 2226–2231.

Gielen V, Johnston SL and Edwards MR (2010) Azithromycin induces anti‐viral responses in bronchial epithelial cells. European Respiratory Journal 36: 646–654.

Glezen WP and Denny FW (1973) Epidemiology of acute lower respiratory disease in children. New England Journal of Medicine 288: 498–505.

Greer RM, McErlean P, Arden KE et al. (2009) Do rhinoviruses reduce the probability of viral co‐detection during acute respiratory tract infections? Journal of Clinical Virology 45: 10–15.

Hendley JO, Edmondson WP Jr and Gwaltney JM Jr (1972) Relation between naturally acquired immunity and infectivity of two rhinoviruses in volunteers. Journal of Infectious Diseases 125: 243–248.

Hendley JO, Wenzel RP and Gwaltney JM Jr (1973) Transmission of rhinovirus colds by self‐inoculation. New England Journal of Medicine 288: 1361–1364.

Hewat EA and Blaas D (2004) Cryoelectron microscopy analysis of the structural changes associated with human rhinovirus type 14 uncoating. Journal of Virology 78: 2935–2942.

Holmes MJ, Reed SE, Stott EJ and Tyrrell DAJ (1976) Studies of experimental rhinovirus type 2 infections in polar isolation and in England. Journal of Hygiene (London) 76: 379–393.

Hughes PJ, North C, Minor PD and Stanway G (1989) The complete nucleotide sequence of Coxsackievirus A21. Journal of General Virology 70: 2943–2952.

Johnston NW, Johnston SL, Norman GR, Dai J and Sears MR (2006) The September epidemic of asthma hospitalization: school children as disease vectors. Journal of Allergy and Clinical Immunology 117: 557–562.

Kaiser L, Aubert J‐D, Pache J‐C et al. (2006) Chronic rhinoviral infection in lung transplant recipients. American Journal of Respiratory and Critical Care Medicine 174: 1392–1399.

van Kempen M, Bachert C and van Cauwenberge P (1999) An update on the pathophysiology of rhinovirus upper respiratory tract infections. Rhinology 37: 97–103.

Ketler A, Hamparian VV and Hilleman MR (1962) Characterization and classification of ECHO 28‐rhinovirus–coryzavirus agents. Proceedings of the Society for Experimental Biology and Medicine 110: 821–831.

Khan AG, Pichler J, Rosemann A and Blaas D (2008) Human rhinovirus type 54 infection via heparan sulfate is less efficient and strictly dependent on low endosomal pH. Journal of Virology 81: 4625–4632.

Kuhn RJ and Rossmann MG (2002) Interaction of major group rhinoviruses with their cellular receptor, ICAM‐1. In: Semler BL and Wimmer E (eds) Molecular Biology of Picornaviruses, pp. 85–92. Washington, DC: ASM Press.

Lambert SB, Allen KM, Carter RC and Nolan TM (2008) The cost of community‐managed viral respiratory illnesses in a cohort of healthy preschool‐aged children. Respiratory Research 9: 1–11.

Lau SKP, Yip CCY, Tsoi H‐W et al. (2007) Clinical features and complete genome characterization of a distinct human rhinovirus genetic cluster, probably representing a previously undetected HRV species, HRV‐C, associated with acute respiratory illness in children. Journal of Clinical Microbiology 45: 3655–3664.

Lu X, Holloway B, Dare RK et al. (2008) Real‐time reverse transcription‐PCR assay for comprehensive detection of human rhinoviruses. Journal of Clinical Microbiology 46: 533–539.

Mackay IM (2008) Human rhinoviruses: the cold wars resume. Journal of Clinical Virology 42: 297–320.

Mackay IM, Arden KE, Nissen MD and Sloots TP (2007) Challenges facing real‐time PCR characterization of acute respiratory tract infections. In: Real‐Time PCR in Microbiology: From Diagnosis to Characterization, pp. 269–318. Norfolk: Caister Academic Press.

Macnaughton MR (1982) The structure and replication of rhinoviruses. Current Topics in Microbiology and Immunology 97: 1–26.

Martin JG, Siddiqui S and Hassan M (2006) Immune responses to viral infections: relevance for asthma. Paediatric Respiratory Reviews 7S: S125–S127.

McErlean P, Shackelton LA, Andrewes E et al. (2008) Distinguishing molecular features and clinical characteristics of a putative new rhinovirus species, human rhinovirus C (HRV C). PLoS One 3: e1847.

McErlean P, Shackelton LA, Lambert SB et al. (2007) Characterisation of a newly identified human rhinovirus, HRV‐QPM, discovered in infants with bronchiolitis. Journal of Clinical Virology 39: 67–75.

Mendell MJ, Fisk WJ, Kreiss K et al. (2002) Improving the health of workers in indoor environments: priority research needs for a national occupational research agenda. American Journal of Public Health 92: 1430–1440.

Papadopoulos NG, Sanderson G, Hunter J and Johnston SL (1999) Rhinoviruses replicate effectively at lower airway temperatures. Journal of Medical Virology 58: 100–104.

Papadopoulos NG, Stanciu LA, Papi A, Holgate ST and Johnston SL (2002) A defective type 1 response to rhinovirus in atopic asthma. Thorax 57: 328–332.

Patick AK, Brothers MA, Maldonado F et al. (2005) In vitro antiviral activity and single‐dose pharmacokinetics in humans of a novel, orally bioavailable inhibitor of human rhinovirus 3C protease. Antimicrobial Agents and Chemotherapy 49: 2267–2275.

Peltola V, Waris M, Österback R et al. (2008) Rhinovirus transmission within families with children: incidence of symptomatic and asymptomatic infections. Journal of Infectious Diseases 197: 382–389.

Pierangeli A, Scagnolari C, Gentile M et al. (2010) Virological diagnosis of respiratory virus infection in patients attending an emergency department during the influenza season. Clinical Microbiology and Infection 16: 391–393.

Purcell K and Fergie J (2002) Concurrent serious bacterial infections in 2396 infants and children hospitalized with respiratory syncytial virus lower respiratory tract infections. Archives of Pediatrics & Adolescent Medicine 156: 322–324.

Quiner CA and Jackson WT (2010) Fragmentation of the Golgi apparatus provides replication membranes for human rhinovirus 1A. Virology 407: 185–195.

Racaniello VR (2001) Picornaviridae: the viruses and their replication. In: Knipe DM and Howley PM (eds) Fields Virology, 4th edn, pp. 685–722. Philadelphia: Lippincott‐Raven.

Rakes GP, Arruda E, Ingram JM et al. (1999) Rhinovirus and respiratory syncytial virus in wheezing children requiring emergency care. American Journal of Respiratory and Critical Care Medicine 159: 785–790.

Rohde G, Wiethege A, Borg I et al. (2003) Respiratory viruses in exacerbations of chronic obstructive pulmonary disease requiring hospitalisation: a case–control study. Thorax 58: 37–42.

Rosenbaum MJ, De Berry P, Sullivan EJ et al. (1971) Epidemiology of the common cold in military recruits with emphasis on infections by rhinovirus types 1A, 2, and two unclassified rhinoviruses. American Journal of Epidemiology 93: 183–193.

Rosenthal LA, Avila PC, Heymann PW et al. (2010) Viral respiratory tract infections and asthma: the course ahead. Journal of Allergy and Clinical Immunology 125: 1212–1217.

Rossmann MG, Arnold E, Erickson JW et al. (1985) Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 317: 145–153.

Rossmann MG, He Y and Kuhn RJ (2002) Picornavirus–receptor interactions. Trends in Microbiology 10: 324–331.

Rotbart HA and Hayden FG (2000) Picornavirus infections: a primer for the practitioner. Archives of Family Medicine 9: 913–920.

Rueckert RR (1996) Picornaviridae: the viruses and their replication. In: Fields BN, Knipe DM and Howley PM (eds) Fields Virology, 3rd edn, pp. 609–654. Philadelphia: Lippincott‐Raven.

Rueckert RR and Wimmer E (1984) Systematic nomenclature of picornavirus proteins. Journal of Virology 50: 957–959.

Ruuskanen O, Lahti E, Jennings LC and Murdoch DR (2011) Viral pneumonia. Lancet 377: 1264–1275.

Simmonds P, McIntyre CL, Savolainen‐Kopra C et al. (2010) Proposals for the classification of human rhinovirus species C into genotypically assigned types. Journal of General Virology 91: 2409–2419.

Stott EJ and Killington RA (1972) Rhinoviruses. Annual Review of Microbiology 26: 503–524.

Tapparel C, Cordey S, Van Belle S et al. (2009) New molecular detection tools adapted to emerging rhinoviruses and enteroviruses. Journal of Clinical Microbiology 47: 1742–1749.

Tovey ER and Rawlinson WD (2011) A modern miasma hypothesis and back‐to‐school asthma exacerbations. Medical Hypotheses 76: 113–116.

Vlasak M, Blomqvist S, Hovi T, Hewat E and Blaas D (2003) Sequence and structure of human rhinoviruses reveal the basis of receptor discrimination. Journal of Virology 77: 6923–6930.

Winther B, Gwaltney JM Jr, Mygind N, Turner RB and Hendley JO (1986) Sites of rhinovirus recovery after point inoculation of the upper airway. JAMA 256: 1763–1767.

Winther B, Hayden FG and Hendley JO (2006) Picornavirus infections in children diagnosed by RT‐PCR during longitudinal surveillance with weekly sampling: association with symptomatic illness and effect of season. Journal of Medical Virology 78: 644–650.

Wisdom A, McWilliam Leitch EC et al. (2009) Screening and comprehensive VP4/2‐typing of human rhinoviruses (HRVs) and enteroviruses: comprehensive VP4‐VP2 typing reveals high incidence and genetic diversity HRV Species C. Journal of Clinical Microbiology 47: 3958–3967.

Further Reading

Mackay IM (2009) Respiratory viruses and the PCR revolution. In: Bustin S (ed.) The PCR Revolution, 1st edn, pp. 189–211. New York: Cambridge University Press.

Mackay IM, Arden KE and Lambert SB (2009) Epidemiology. In: Eccles R and Weber O (eds) Common Cold, pp. 77–106. Berlin: Springer.

Tyrrell DAJ (1992) A view from the common cold unit. Antiviral Research 18: 105–125.

Tyrrell DAJ, Bynoe ML, Hitchcock G, Pereira HG and Andrewes CH (1960) Some virus isolations from common colds. I. Experiments employing human volunteers. Lancet 1: 235–237.

Tyrrell DAJ and Fielder M (2002) Cold Wars: The Fight against the Common Cold. New York: Oxford University Press.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Arden, Katherine E, and Mackay, Ian M(Aug 2011) Rhinoviruses. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000431.pub3]