Chapter 47 : Rhinovirus

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Rhinoviruses (RVs), members of the family (1), constitute the largest group of respiratory viruses. RVs are recognized as causing more than 50% of all acute respiratory infections and represent the single most important causative agent of common colds. The name “rhinovirus” stems from the virus's special adaptation to infect the nasopharynx. It was already known in 1930 that “colds” were easily transmitted from human to human and to apes, and that the responsible agent was probably a virus (2, 3), but it was not until 1956 that the first RV was discovered by isolation in cell culture (4, 5). The discovery of the low temperature optimum (32–35°C) for viral replication (6), the development of sensitive primary human embryonic lung cell cultures (WI-38 and MRC-5), and the continuous H1-Hela cell line (7, 8) facilitated the isolation, classification, and epidemiological and biological studies of RVs. A total of 100 serotypes were identified over the next 30 years (9). The first complete genome sequence was determined for RV14 in 1984 (10), a reverse genetics system was developed in 1985 (11), and the X-ray crystallographic structures of the viral capsids of five serotypes (1A, 2, 3, 14, and 16) were solved soon afterward (12–17). The recent use of more sensitive RT-PCR-based molecular assays for RV identification has generated clear evidence that RV infections are also common causes of more severe lower respiratory illnesses, such as bronchiolitis, pneumonia, exacerbations of asthma, and other chronic lung diseases (18–22). RT-PCR has also led to the discovery of more than 50 genotypes of previously unrecognized RVs that belong to a new species (RV-C). These viruses escaped traditional culture-based detection (23–26). This discovery has promoted a new wave of interest in RV research.

Citation: Lee W, Gern J. 2017. Rhinovirus, p 1143-1164. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch47
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Image of FIGURE 1

Receptor groups of rhinoviruses. Majority of RV serotypes (63 RV-A and all 25 RV-B) use ICAM-1 as the receptor. The remaining 12 RV-A serotypes bind to low-density lipoprotein receptor (LDLR) family proteins. RV87 was originally misidentified as a RV and has been reclassified as an enterovirus (EV-D68). The receptor for RV-C has been recently identified as cadherin-related family member 3 (CDHR3) protein.

Citation: Lee W, Gern J. 2017. Rhinovirus, p 1143-1164. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch47
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Image of FIGURE 2

(A) Schematic drawing of ICAM-1, the receptor used by the major group RVs. S-S represents disulfide bridges, and small circles represent sites of glycosylation. (B) Key features of the structure of a human RV. The virion shell consists of 12 pentamers, one of which has been removed to show the approximate location of the RNA packed tightly into a central cavity. Each pentamer, in turn, consists of five wedge-shaped protomer subunits. The canyon (shaded) is shown encircling the five-fold axis of the pentamer; the hydrophobic (drug-binding) pocket is indicated below the floor of the canyon in VP1. (C) A side view of the pentamer showing the spatial relationship between the receptor-binding site and the hydrophobic pocket. An ion, located at each pentamer center in serotypes 1A, 14, and 16 is tentatively identified as calcium.

Citation: Lee W, Gern J. 2017. Rhinovirus, p 1143-1164. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch47
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Image of FIGURE 3

(A) RNA genome of a human RV. P1, P2, and P3 refer to precursor proteins that are subsequently processed to produce 11 end products. (B) Cleavage of the polyprotein is accomplished by two viral proteases, 2A and 3C. The 2A protease co-translationally releases the coat precursor, P1, from nascent polyprotein, whereas the 3C (or precursor 3CD) protease cleaves all the remaining precursors and intermediates except for VP0 (1A-1B). Cleavage of VP0 to VP4 (1A) and VP2 (1B), maturation cleavage, occurs only after the RNA has been packaged in the protein shell. The VP0 cleavage site lies buried inside the shell near the RNA; the active site for this cleavage is not yet precisely known and might include bases in the RNA genome. The amino termini of coat proteins P1 and VP4 are blocked by a myristoyl group. Cis-cleavage of the N-terminus of 2A is shown by an arrow; black triangles indicate 3C cleavage sites.

Citation: Lee W, Gern J. 2017. Rhinovirus, p 1143-1164. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch47
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Image of FIGURE 4

(A) Diagram representing virion architecture and assembly. (B) The mature virion contains four major proteins (VP1 [1D], 2 [1B], 3 [1C], and 4 [1A],) plus traces of VP0, representing residual precursor following the maturation cleavage required for acquisition of infectivity.

Citation: Lee W, Gern J. 2017. Rhinovirus, p 1143-1164. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch47
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Image of FIGURE 5

Overview of the RV infection cycle.

Citation: Lee W, Gern J. 2017. Rhinovirus, p 1143-1164. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch47
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Image of FIGURE 6

Cytopathic effect (CPE) in H1-Hela and WI-38 cells caused by RV infection. Cells were exposed to 100 PFU of human RV type 16 (RV16) per cell and incubated at 35°C. Infected HeLa cells became rounded and detached from growth surface by 12 hours but WI-38 cells required 48 hours to develop CPE.

Citation: Lee W, Gern J. 2017. Rhinovirus, p 1143-1164. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch47
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Image of FIGURE 7

Proposed pathogenesis of symptoms associated with RV infection.

Citation: Lee W, Gern J. 2017. Rhinovirus, p 1143-1164. In Richman D, Whitley R, Hayden F (ed), Clinical Virology, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819439.ch47
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1. King AMQ, Adams MJ, Carstens EB, Lefkowitz EJ . 2012. Picornaviridae, p 855 880. In Virus Taxonomy: Classification and Nomenclature of Viruses: Ninth Report of the International Committee on Taxonomy of Viruses. Elsevier Academic Press, San Diego, CA.
2. Dochez AR, Shibley GS, Mills KC . 1930. Studies on the common cold. IV. Experimental transmission of the common cold to anthropoid apes and human beings by means of a filtrable agent. J Exp Med 52 : 701 716.[PubMed]
3. Kruse W . 1914. Die Errger van Husten and Schupfen. Munch Med Wochenschr 61 : 1547 1552.
4. Pelon W, Mogabgab WJ, Phillips IA, Pierce WE . 1957. A cytopathogenic agent isolated from naval recruits with mild respiratory illnesses. Proc Soc Exp Biol Med 94 : 262 267.[PubMed]
5. Price WH . 1956. The isolation of a new virus associated with respiratory clinical disease in humans. Proc Natl Acad Sci USA 42 : 892 896.[PubMed]
6. Tyrrell DA, Parsons R . 1960. Some virus isolations from common colds. III. Cytopathic effects in tissue cultures. Lancet 275 : 239 242.[PubMed]
7. Conant RM, Somerson NL, Hamparian VV . 1968. Plaque formation by rhinoviruses. Proc Soc Exp Biol Med 128 : 51 56.[PubMed]
8. Ketler A, Hamparian VV, Hilleman MR . 1962. Characterization and classification of ECHO 28-rhinovirus-coryzavirus agents. Proc Soc Exp Biol Med 110 : 821 831.[PubMed]
9. Hamparian VV . , et al . 1987. A collaborative report: rhinoviruses—extension of the numbering system from 89 to 100. Virology 159 : 191 192.[PubMed]
10. Stanway G, Hughes PJ, Mountford RC, Minor PD, Almond JW . 1984. The complete nucleotide sequence of a common cold virus: human rhinovirus 14. Nucleic Acids Res 12 : 7859 7875. [PubMed]
11. Mizutani S, Colonno RJ . 1985. In vitro synthesis of an infectious RNA from cDNA clones of human rhinovirus type 14. J Virol 56 : 628 632.[PubMed]
12. Hadfield AT, Lee W, Zhao R, Oliveira MA, Minor I, Rueckert RR, Rossmann MG . 1997. The refined structure of human rhinovirus 16 at 2.15 A resolution: implications for the viral life cycle. Structure 5 : 427 441.[PubMed]
13. Kim SS, Smith TJ, Chapman MS, Rossmann MC, Pevear DC, Dutko FJ, Felock PJ, Diana GD, McKinlay MA . 1989. Crystal structure of human rhinovirus serotype 1A (HRV1A). J Mol Biol 210 : 91 111.[PubMed]
14. Oliveira MA, Zhao R, Lee W-M, Kremer MJ, Minor I, Rueckert RR, Diana GD, Pevear DC, Dutko FJ, McKinlay MA, Rossmann MG . 1993. The structure of human rhinovirus 16. Structure 1 : 51 68.[PubMed]
15. Rossmann MG, Arnold E, Erickson JW, Frankenberger EA, Griffith JP, Hecht H-J, Johnson JE, Kamer G, Luo M, Mosser AG, Rueckert R, Sherry B, Vriend G . 1985. Structure of a human common cold virus and its functional relations to other picornaviruses. Nature 317 : 145 153.[PubMed]
16. Verdaguer N, Blaas D, Fita I . 2000. Structure of human rhinovirus serotype 2 (HRV2). J Mol Biol 300 : 1179 1194.[PubMed]
17. Zhao R, Pevear DC, Kremer MJ, Giranda VL, Kofron JA, Kuhn RJ, Rossmann MG . 1996. Human rhinovirus 3 at 3.0 A resolution. Structure 4 : 1205 1220.[PubMed]
18. Busse WW, Lemanske RF Jr, Gern JE . 2010. Role of viral respiratory infections in asthma and asthma exacerbations. Lancet 376 : 826 834.[PubMed]
19. Hershenson MB . 2013. Rhinovirus-induced exacerbations of asthma and COPD. Scientifica (Cairo) 2013 : 405876.[PubMed]
20. Iwane MK, Prill MM, Lu X, Miller EK, Edwards KM, Hall CB, Griffin MR, Staat MA, Anderson LJ, Williams JV, Weinberg GA, Ali A, Szilagyi PG, Zhu Y, Erdman DD . 2011. Human rhinovirus species associated with hospitalizations for acute respiratory illness in young US children. J Infect Dis 204 : 1702 1710.[PubMed]
21. Jartti T, Korppi M . 2011. Rhinovirus-induced bronchiolitis and asthma development. Pediatr Allergy Immunol 22 : 350 355.[PubMed]
22. Ruuskanen O, Waris M, Ramilo O . 2013. New aspects on human rhinovirus infections. Pediatr Infect Dis J 32 : 553 555.[PubMed]
23. Lamson D, Renwick N, Kapoor V, Liu Z, Palacios G, Ju J, Dean A, St George K, Briese T, Lipkin WI . 2006. MassTag polymerase-chain-reaction detection of respiratory pathogens, including a new rhinovirus genotype, that caused influenza-like illness in New York State during 2004–2005. J Infect Dis 194 : 1398 1402.[PubMed]
24. Lau SK, Yip CC, Tsoi HW, Lee RA, So LY, Lau YL, Chan KH, Woo PC, Yuen KY . 2007. Clinical features and complete genome characterization of a distinct human rhinovirus (HRV) genetic cluster, probably representing a previously undetected HRV species, HRV-C, associated with acute respiratory illness in children. J Clin Microbiol 45 : 3655 3664.[PubMed]
25. Lee WM, Kiesner C, Pappas T, Lee I, Grindle K, Jartti T, Jakiela B, Lemanske RF Jr, Shult PA, Gern JE . 2007. A diverse group of previously unrecognized human rhinoviruses are common causes of respiratory illnesses in infants. PLoS One 2 : e966.[PubMed]
26. McErlean P, Shackelton LA, Lambert SB, Nissen MD, Sloots TP, Mackay IM . 2007. Characterisation of a newly identified human rhinovirus, HRV-QPM, discovered in infants with bronchiolitis. J Clin Virol 39 : 67 75.[PubMed]
27. Stanway G, Brown F, Christian P, Hovi T, Hyypiä T, King AMQ, Knowles NJ, Lemon SM, Minor PD, Pallansch MA, Palmenberg AC, and Skern T, . 2005. Picornaviridae, p 757 778. In Fauquet CM, Mayo MA, Maniloff J, Dusellberger U, Ball LA (eds), Virus Taxonomy: Eighth Report of the International Committee on Taxonomy of Viruses. Elsevier Academic Press, San Diego, California.
28. Conant RM, Hamparian VV . 1968. Rhinoviruses: basis for a numbering system. II. Serologic characterization of prototype strains. J Immunol 100 : 114 119.[PubMed]
29. Cooney MK, Fox JP, Kenny GE . 1982. Antigenic groupings of 90 rhinovirus serotypes. Infect Immun 37 : 642 647.[PubMed]
30. Patterson LJ, Hamparian VV . 1997. Hyper-antigenic variation occurs with human rhinovirus type 17. J Virol 71 : 1370 1374.[PubMed]
31. He Y, Mueller S, Chipman PR, Bator CM, Peng X, Bowman VD, Mukhopadhyay S, Wimmer E, Kuhn RJ, Rossmann MG . 2003. Complexes of poliovirus serotypes with their common cellular receptor, CD155. J Virol 77 : 4827 4835.[PubMed]
32. Horsnell C, Gama RE, Hughes PJ, Stanway G . 1995. Molecular relationships between 21 human rhinovirus serotypes. J Gen Virol 76 : 2549 2555.[PubMed]
33. Kistler AL, Webster DR, Rouskin S, Magrini V, Credle JJ, Schnurr DP, Boushey HA, Mardis ER, Li H, DeRisi JL . 2007. Genome-wide diversity and selective pressure in the human rhinovirus. Virol J 4 : 40.[PubMed]
34. Palmenberg AC, Spiro D, Kuzmickas R, Wang S, Djikeng A, Rathe JA, Fraser-Liggett CM, Liggett SB . 2009. Sequencing and analyses of all known human rhinovirus genomes reveal structure and evolution. Science 324 : 55 59.[PubMed]
35. Tapparel C, Junier T, Gerlach D, Cordey S, Van Belle S, Perrin L, Zdobnov EM, Kaiser L . 2007. New complete genome sequences of human rhinoviruses shed light on their phylogeny and genomic features. BMC Genomics 8 : 224.[PubMed]
36. Linder JE, Kraft DC, Mohamed Y, Lu Z, Heil L, Tollefson S,, Saville BR, Wright PF,, Williams JV, Miller EK . 2012. Human rhinovirus C: Age, season, and lower respiratory illness over the past 3 decades. J Allergy Clin Immunol 131(1): 69 77.
37. ICTV Picornaviridae Study Group . 2015. Rhinovirus C. Available at: http://www.picornastudygroup.com/types/enterovirus/hrv-c.htm. Accessed 22 June 2015.
38. Ashraf S, Brockman-Schneider R, Bochkov YA, Pasic TR, Gern JE . 2013. Biological characteristics and propagation of human rhinovirus-C in differentiated sinus epithelial cells. Virology 436 : 143 149.[PubMed]
39. Bochkov YA, Palmenberg AC, Lee WM, Rathe JA, Amineva SP, Sun X, Pasic TR, Jarjour NN, Liggett SB, Gern JE . 2011. Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C. Nat Med 17 : 627 632.[PubMed]
40. Bochkov YA, Watters K, Ashraf S, Griggs TF, Devries MK, Jackson DJ, Palmenberg AC, Gern JE . 2015. Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication. Proc Natl Acad Sci USA 112 : 5485 5490.[PubMed]
41. Hao W, Bernard K, Patel N, Ulbrandt N, Feng H, Svabek C, Wilson S, Stracener C, Wang K, Suzich J, Blair W, Zhu Q . 2012. Infection and propagation of human rhinovirus C in human airway epithelial cells. J Virol 86 : 13524 13532.[PubMed]
42. Tapparel C, Sobo K, Constant S, Huang S, Van Belle S, Kaiser L . 2013. Growth and characterization of different human rhinovirus C types in three-dimensional human airway epithelia reconstituted in vitro. Virology 446 : 1 8.[PubMed]
43. Greve JM, Davis G, Meyer AM, Forte CP, Yost SC, Marlor CW, Kamarck ME, McClelland A . 1989. The major human rhinovirus receptor is ICAM-1. Cell 56 : 839 847.[PubMed]
44. Reithmayer M, Reischl A, Snyers L, Blaas D . 2002. Species-specific receptor recognition by a minor-group human rhinovirus (HRV): HRV serotype 1A distinguishes between the murine and the human low-density lipoprotein receptor. J Virol 76 : 6957 6965.[PubMed]
45. Vlasak M, Roivainen M, Reithmayer M, Goesler I, Laine P, Snyers L, Hovi T, Blaas D . 2005. The minor receptor group of human rhinovirus (HRV) includes HRV23 and HRV25, but the presence of a lysine in the VP1 HI loop is not sufficient for receptor binding. J Virol 79 : 7389 7395.[PubMed]
46. Lee WM, Chen Y, Wang W, Mosser A . 2015. Growth of human rhinovirus in H1-HeLa cell suspension culture and purification of virions. Methods Mol Biol 1221 : 49 61.[PubMed]
47. Rueckert R, . 1996. Picornaviridae: the viruses and their replication, p 609 654. In Fields BN, Knipe DM, Howley PM, , et al (eds) Virology, ed 3. Lippincott-Raven Publishers, Philadelphia.
48. Colonno RJ, Condra JH, Mizutani S, Callahan PL, Davies ME, Murcko MA . 1988. Evidence for the direct involvement of the rhinovirus canyon in receptor binding. Proc Natl Acad Sci USA 85 : 5449 5453.[PubMed]
49. Olson NH, Kolatkar PR, Oliveira MA, Cheng RH, Greve JM, McClelland A, Baker TS, Rossmann MG . 1993. Structure of a human rhinovirus complexed with its receptor molecule. Proc Natl Acad Sci USA 90 : 507 511.[PubMed]
50. Rossmann MG . 1989. The canyon hypothesis. Hiding the host cell receptor attachment site on a viral surface from immune surveillance. J Biol Chem 264 : 14587 14590.[PubMed]
51. Smith TJ, Chase ES, Schmidt TJ, Olson NH, Baker TS . 1996. Neutralizing antibody to human rhinovirus 14 penetrates the receptor-binding canyon. Nature 383 : 350 354.[PubMed]
52. Verdaguer N, Fita I, Reithmayer M, Moser R, Blaas D . 2004. X-ray structure of a minor group human rhinovirus bound to a fragment of its cellular receptor protein. Nat Struct Mol Biol 11 : 429 434.[PubMed]
53. Katpally U, Smith TJ . 2007. Pocket factors are unlikely to play a major role in the life cycle of human rhinovirus. J Virol 81 : 6307 6315.[PubMed]
54. Lee WM, Wang W . 2003. Human rhinovirus type 16: mutant V1210A requires capsid-binding drug for assembly of pentamers to form virions during morphogenesis. J Virol 77 : 6235 6244.[PubMed]
55. Fox MP, Otto MJ, McKinlay MA . 1986. Prevention of rhinovirus and poliovirus uncoating by WIN 51711, a new antiviral drug. Antimicrob Agents Chemother 30 : 110 116.[PubMed]
56. Heinz BA, Rueckert RR, Shepard DA, Dutko FJ, McKinlay MA, Fancher M, Rossmann MG, Badger J, Smith TJ . 1989. Genetic and molecular analyses of spontaneous mutants of human rhinovirus 14 that are resistant to an antiviral compound. J Virol 63 : 2476 2485.[PubMed]
57. Basta HA, Ashraf S, Sgro JY, Bochkov YA, Gern JE, Palmenberg AC . 2014. Modeling of the human rhinovirus C capsid suggests possible causes for antiviral drug resistance. Virology 448 : 82 90.[PubMed]
58. Mosser AG, Leippe DM, Rueckert RR, . 1989. Neutralization of picornaviruses: Support for the pentamer bridging hypothesis, p 155 168. In Semler B, Ehrenfeld E (eds), Molecular Aspects of Picornavirus Infection and Detection. American Society for Microbiology, Washington, D.C.
59. Smith TJ, Baker T . 1999. Picornaviruses: epitopes, canyons, and pockets. Adv Virus Res 52 : 1 23. [PubMed]
60. Brown DM, Cornell CT, Tran GP, Nguyen JH, Semler BL . 2005. An authentic 3′ noncoding region is necessary for efficient poliovirus replication. J Virol 79 : 11962 11973.[PubMed]
61. Lee WM, Monroe SS, Rueckert RR . 1993. Role of maturation cleavage in infectivity of picornaviruses: activation of an infectosome. J Virol 67 : 2110 2122.[PubMed]
62. Hoover-Litty H, Greve JM . 1993. Formation of rhinovirus-soluble ICAM-1 complexes and conformational changes in the virion. J Virol 67 : 390 397.[PubMed]
63. Lau C, Wang X, Song L, North M, Wiehler S, Proud D, Chow CW . 2008. Syk associates with clathrin and mediates phosphatidylinositol 3-kinase activation during human rhinovirus internalization. J Immunol 180 : 870 880.[PubMed]
64. Snyers L, Zwickl H, Blaas D . 2003. Human rhinovirus type 2 is internalized by clathrin-mediated endocytosis. J Virol 77 : 5360 5369.[PubMed]
65. Barton DJ, Morasco BJ, Flanegan JB . 1999. Translating ribosomes inhibit poliovirus negative-strand RNA synthesis. J Virol 73 : 10104 10112.[PubMed]
66. Novak JE, Kirkegaard K . 1991. Improved method for detecting poliovirus negative strands used to demonstrate specificity of positive-strand encapsidation and the ratio of positive to negative strands in infected cells. J Virol 65 : 3384 3387.[PubMed]
67. Paul AV, Rieder E, Kim DW, van Boom JH, Wimmer E . 2000. Identification of an RNA hairpin in poliovirus RNA that serves as the primary template in the in vitro uridylylation of VPg. J Virol 74 : 10359 10370.[PubMed]
68. Cordey S, Gerlach D, Junier T, Zdobnov EM, Kaiser L, Tapparel C . 2008. The cis-acting replication elements define human enterovirus and rhinovirus species. RNA 14 : 1568 1578.[PubMed]
69. McKnight KL . 2003. The human rhinovirus internal cis-acting replication element (cre) exhibits disparate properties among serotypes. Arch Virol 148 : 2397 241. [PubMed]
70. Nugent CI, Johnson KL, Sarnow P, Kirkegaard K . 1999. Functional coupling between replication and packaging of poliovirus replicon RNA. J Virol 73 : 427 435.[PubMed]
71. Ali IK, McKendrick L, Morley SJ, Jackson RJ . 2001. Truncated initiation factor eIF4G lacking an eIF4E binding site can support capped mRNA translation. EMBO J 20 : 4233 4242.[PubMed]
72. Dick EC, Dick CR . 1974. Natural and experimental infections of nonhuman primates with respiratory viruses. Lab Anim Sci 24 : 177 181.[PubMed]
73. Pinto CA, Bahnsen HP, Ravin LJ, Haff RF, Pagano JF . 1972. The antiviral effect of a triazinoindole (SK&F 40491) in rhinovirus infected gibbons. Proc Soc Exp Biol Med 141 : 467 474.[PubMed]
74. Harris JR, Racaniello VR . 2003. Changes in rhinovirus protein 2C allow efficient replication in mouse cells. J Virol 77 : 4773 4780.[PubMed]
75. Rasmussen AL, Racaniello VR . 2011. Selection of rhinovirus 1A variants adapted for growth in mouse lung epithelial cells. Virology 420 : 82 88.[PubMed]
76. Tuthill TJ, Papadopoulos NG, Jourdan P, Challinor LJ, Sharp NA, Plumpton C, Shah K, Barnard S, Dash L, Burnet J, Killington RA, Rowlands DJ, Clarke NJ, Blair ED, Johnston SL . 2003. Mouse respiratory epithelial cells support efficient replication of human rhinovirus. J Gen Virol 84 : 2829 2836.[PubMed]
77. Wang W . 1997. Chapter 2: Evidence that the drug-dependent mutants are assembly defective, p 51 70. In Human Rhinovirus-16: Characterization of Mutants Requiring Capsid-binding Win Drugs for Growth. University of Wisconsin, Madison.
78. Bartlett NW, Walton RP, Edwards MR, Aniscenko J, Caramori G, Zhu J, Glanville N, Choy KJ, Jourdan P, Burnet J, Tuthill TJ, Pedrick MS, Hurle MJ, Plumpton C, Sharp NA, Bussell JN, Swallow DM, Schwarze J, Guy B, Almond JW, Jeffery PK, Lloyd CM, Papi A, Killington RA, Rowlands DJ, Blair ED, Clarke NJ, Johnston SL . 2008. Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation. Nat Med 14 : 199 204. [PubMed]
79. Newcomb DC, Sajjan US, Nagarkar DR, Wang Q, Nanua S, Zhou Y, McHenry CL, Hennrick KT, Tsai WC, Bentley JK, Lukacs NW, Johnston SL, Hershenson MB . 2008. Human rhinovirus 1B exposure induces phosphatidylinositol 3-kinase-dependent airway inflammation in mice. Am J Respir Crit Care Med 177 : 1111 1121.[PubMed]
80. Rasmussen AL . 2009. Chapter 3: Development and characterization of human ICAM-1 transgenic mice and susceptibility to mouse-adapted RV16/L and RV39/L, p 33 47. In Development of a mouse model of rhinovirus infection. Columbia University, New York.
81. Shaw R,, Sowa M, Pedrick M, Fife M, Nials A, Knowles R, Hessel E . 2013. Strategies to mimic virally induced asthmatic exacerbations: the use of rhinovirus and influenza in acute and chronic mouse models. J Inflamm 10 (Suppl 1) :Poster 19.
82. Zhu L, Lee PK, Lee WM, Zhao Y, Yu D, Chen Y . 2009. Rhinovirus-induced major airway mucin production involves a novel TLR3-EGFR-dependent pathway. Am J Respir Cell Mol Biol 40 : 610 619.[PubMed]
83. Lee WM, Chen Y, Wang W, Mosser A . 2015. Infectivity assays of human rhinovirus-A and -B serotypes. Methods Mol Biol 1221 : 71 81.[PubMed]
84. Chen Y, Hamati E, Lee PK, Lee WM, Wachi S, Schnurr D, Yagi S, Dolganov G, Boushey H, Avila P, Wu R . 2006. Rhinovirus induces airway epithelial gene expression through double-stranded RNA and IFN-dependent pathways. Am J Respir Cell Mol Biol 34 : 192 203. [PubMed]
85. Wu R, Zhao YH, Chang MM . 1997. Growth and differentiation of conducting airway epithelial cells in culture. Eur Respir J 10 : 2398 2403.[PubMed]
86. Mosser AG, Rueckert RR, . 1996. Picornavirus capsid binding agents, p 13 40. In Richman DD (ed), Antiviral Drug Resistance. John Wiley & Sons, Ltd, New York.
87. Griggs TF, Bochkov YA, Nakagome K, Palmenberg AC, Gern JE . 2015. Production, purification, and capsid stability of rhinovirus C types. J Virol Methods 217 : 18 23.[PubMed]
88. Gwaltney JM Jr, Moskalski PB, Hendley JO . 1980. Interruption of experimental rhinovirus transmission. J Infect Dis 142 : 811 815.[PubMed]
89. Thwing CJ, Arruda E, Vieira Filho JP,, Castelo Filho A, Gwaltney JM Jr. 1993. Rhinovirus antibodies in an isolated Amazon Indian tribe. Am J Trop Med Hyg 48: 771 775.
90. Winther B, Hayden FG, 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. J Med Virol 78 : 644 650.[PubMed]
91. Byington CL, Ampofo K, Stockmann C, Adler FR, Herbener A, Miller T, Sheng X, Blaschke AJ, Crisp R, Pavia AT . 2015. Community surveillance of respiratory viruses among families in the Utah Better Identification of Germs-Longitudinal Viral Epidemiology (BIG-LoVE) Study. Clin Infect Dis 61 : 1217 1224.[PubMed]
92. Jartti T, Lehtinen P, Vuorinen T, Koskenvuo M, Ruuskanen O . 2004. Persistence of rhinovirus and enterovirus RNA after acute respiratory illness in children. J Med Virol 72 : 695 699.[PubMed]
93. Jartti T, Lee WM, Pappas T, Evans M, Lemanske RF Jr, Gern JE . 2008. Serial viral infections in infants with recurrent respiratory illnesses. Eur Respir J 32 : 314 320.[PubMed]
94. Olenec JP, Kim WK, Lee WM, Vang F, Pappas TE, Salazar LE, Evans MD, Bork J, Roberg K, Lemanske RF Jr, Gern JE . 2010. Weekly monitoring of children with asthma for infections and illness during common cold seasons. J Allergy Clin Immunol 125 : 1001 1006.[PubMed]
95. Tapparel C, Cordey S, Junier T, Farinelli L, Van Belle S, Soccal PM, Aubert JD, Zdobnov E, Kaiser L . 2011. Rhinovirus genome variation during chronic upper and lower respiratory tract infections. PLoS One 6 : e21163.[PubMed]
96. Lee WM, Lemanske RF Jr, Evans MD, Vang F, Pappas T, Gangnon R, Jackson DJ, Gern JE . 2012. Human rhinovirus species and season of infection determine illness severity. Am J Respir Crit Care Med 186 : 886 891.[PubMed]
97. Frost WH, , and M Gover . 1932. The incidence and time distribution of common colds in several groups kept under continuous observation. Public Health Reports 47 : 1815 1841.
98. Dingle JH, Badger GF, Jordan WS Jr. 1964. Illness in the Home: a Study of 25,000 Illnesses in a Group of Cleveland Families. Case Western Reserve University Press, Cleveland, OH.
99. Gwaltney JM Jr, Hendley JO, Simon G, Jordan WS Jr . 1966. Rhinovirus infections in an industrial population. I. The occurrence of illness. N Engl J Med 275 : 1261 1268.[PubMed]
100. Souza LS, Ramos EA, Carvalho FM, Guedes VM, Souza LS, Rocha CM, Soares AB, Velloso LF, Macedo IS, Moura FE, Siqueira M, Fortes S, de Jesus CC, Santiago CM, Carvalho AM, Arruda E . 2003. Viral respiratory infections in young children attending day care in urban Northeast Brazil. Pediatr Pulmonol 35 : 184 191.[PubMed]
101. Gwaltney JM Jr . 1985. The Jeremiah Metzger lecture. Climatology and the common cold. Trans Am Clin Climatol Assoc 96 : 159 175.[PubMed]
102. Sears MR, Johnston NW . 2007. Understanding the September asthma epidemic. J Allergy Clin Immunol 120 : 526 529.[PubMed]
103. Hemmes JH, Winkler KC, Kool SM . 1960. Virus survival as a seasonal factor in influenza and polimyelitis. Nature 188 : 430 431.[PubMed]
104. Johnston NW, Johnston SL, Norman GR, Dai J, Sears MR . 2006. The September epidemic of asthma hospitalization: school children as disease vectors. J Allergy Clin Immunol 117 : 557 562. [PubMed]
105. Hendley JO, Wenzel RP, Gwaltney JM Jr . 1973. Transmission of rhinovirus colds by self-inoculation. N Engl J Med 288 : 1361 1364.[PubMed]
106. D'Alessio DJ, Meschievitz CK, Peterson JA, Dick CR, Dick EC . 1984. Short-duration exposure and the transmission of rhinoviral colds. J Infect Dis 150 : 189 194.[PubMed]
107. Couch RB, Cate TR, Douglas RG Jr, Gerone PJ, Knight V . 1966. Effect of route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission. Bacteriol Rev 30 : 517 529.[PubMed]
108. Douglas RM, Moore BW, Miles HB, Davies LM, Graham NM, Ryan P, Worswick DA, Albrecht JK . 1986. Prophylactic efficacy of intranasal alpha 2-interferon against rhinovirus infections in the family setting. N Engl J Med 314 : 65 70.[PubMed]
109. Dick EC, Jennings LC, Mink KA, Wartgow CD, Inborn SL . 1987. Aerosol transmission of rhinovirus colds. J Infect Dis 156 : 442 448.[PubMed]
110. Hendley JO, Gwaltney JM Jr . 1988. Mechanisms of transmission of rhinovirus infections. Epidemiol Rev 10 : 243 258.[PubMed]
111. Reed SE . 1975. An investigation of the possible transmission of Rhinovirus colds through indirect contact. J Hyg (Lond) 75 : 249 258.[PubMed]
112. Jennings LC, Dick EC, Mink KA, Wartgow CD, Inhorn SL . 1988. Near disappearance of rhinovirus along a fomite transmission chain. J Infect Dis 158 : 888 892.[PubMed]
113. Cortey DL, Gevirtz R, Nideffer R, Cummins L . 1987. Prevention of postinfectious asthma in children by reducing self-inoculatory behavior. J Pediatr Psychol 12 : 519 531.[PubMed]
114. D'Alessio DJ, Peterson JA, Dick CR, Dick EC . 1976. Transmission of experimental rhinovirus colds in volunteer married couples. J Infect Dis 133 : 28 36.[PubMed]
115. Hendley JO, Gwaltney JM Jr, Jordan WS Jr . 1969. Rhinovirus infections in an industrial population. IV. Infections within families of employees during two fall peaks of respiratory illness. Am J Epidemiol 89 : 184 196.[PubMed]
116. Peltola V, Waris M, Osterback R, Susi P, Ruuskanen O, Hyypiä T . 2008. Rhinovirus transmission within families with children: incidence of symptomatic and asymptomatic infections. J Infect Dis 197 : 382 389.[PubMed]
117. Harris JM II, Gwaltney JM Jr . 1996. Incubation periods of experimental rhinovirus infection and illness. Clin Infect Dis 23 : 1287 1290.[PubMed]
118. Message SD, Laza-Stanca V, Mallia P, Parker HL, Zhu J, Kebadze T, Contoli M, Sanderson G, Kon OM, Papi A, Jeffery PK, Stanciu LA, Johnston SL . 2008. Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production. Proc Natl Acad Sci USA 105 : 13562 13567.[PubMed]
119. Arruda E, Boyle TR, Winther B, Pevear DC, Gwaltney JM Jr, Hayden FG . 1995. Localization of human rhinovirus replication in the upper respiratory tract by in situ hybridization. J Infect Dis 171 : 1329 1333.[PubMed]
120. Mosser AG, Vrtis R, Burchell L, Lee WM, Dick CR, Weisshaar E, Bock D, Swenson CA, Cornwell RD, Meyer KC, Jarjour NN, Busse WW, Gern JE . 2005. Quantitative and qualitative analysis of rhinovirus infection in bronchial tissues. Am J Respir Crit Care Med 171 : 645 651.[PubMed]
121. Bentley JK, Sajjan US, Dzaman MB, Jarjour NN, Lee WM, Gern JE,, and Hershenson MB . 2013. Rhinovirus colocalizes with CD68- and CD11b-positive macrophages following experimental infection in humans. J Allergy Clin Immunol 132(3): 758 761.
122. Gern JE, Dick EC, Lee WM, Murray S, Meyer K, Handzel ZT, Busse WW . 1996. Rhinovirus enters but does not replicate inside monocytes and airway macrophages. J Immunol 156 : 621 627.[PubMed]
123. Ghildyal R, Dagher H, Donninger H, de Silva D, Li X, Freezer NJ, Wilson JW, Bardin PG . 2005. Rhinovirus infects primary human airway fibroblasts and induces a neutrophil chemokine and a permeability factor. J Med Virol 75 : 608 615.[PubMed]
124. Handzel ZT, ,. Busse WW, Sedgwick JB,, Vrtis R, Lee WM, ,. Kelly EAB, Gern JE . 1998. Eosinophils bind rhinovirus and activate virus-specific T cells. J Immunol 160: 1279 1284.
125. Winther B, Gwaltney JMJ Jr, Mygind N, Turner RB, Hendley JO . 1986. Sites of rhinovirus recovery after point inoculation of the upper airway. JAMA 256 : 1763 1767.[PubMed]
126. Winther B, Greve JM, Gwaltney JM Jr, Innes DJ, Eastham JR, McClelland A, Hendley JO . 1997. Surface expression of intercellular adhesion molecule 1 on epithelial cells in the human adenoid. J Infect Dis 176 : 523 525.[PubMed]
127. Jakiela B, Gielicz A, Plutecka H, Hubalewska-Mazgaj M, Mastalerz L, Bochenek G, Soja J, Januszek R, Aab A, Musial J, Akdis M, Akdis CA, Sanak M . 2014. Th2-type cytokine-induced mucus metaplasia decreases susceptibility of human bronchial epithelium to rhinovirus infection. Am J Respir Cell Mol Biol 51 : 229 241.[PubMed]
128. Principi N, Zampiero A, Gambino M, Scala A, Senatore L, Lelii M, Ascolese B, Pelucchi C, Esposito S . 2015. Prospective evaluation of rhinovirus infection in healthy young children. J Clin Virol 66 : 83 89.[PubMed]
129. Reid AB, Anderson TL, Cooley L, Williamson J, Mcgregor AR . 2011. An outbreak of human rhinovirus species C infections in a neonatal intensive care unit. Pediatr Infect Dis J 30 : 1096 5.[PubMed]
130. McFadden ER Jr, Pichurko BM, Bowman HF, Ingenito E, Burns S, Dowling N, Solway J . 1985. Thermal mapping of the airways in humans. J Appl Physiol 1985 58 : 564 570.[PubMed]
131. Papadopoulos NG, Sanderson G, Hunter J, Johnston SL . 1999. Rhinoviruses replicate effectively at lower airway temperatures. J Med Virol 58 : 100 104.[PubMed]
132. Lopez-Souza N, Favoreto S, Wong H, Ward T, Yagi S, Schnurr D,, Finkbeiner WE, Dolganov GM, Widdicombe House JH, Avila PC. 2009. In vitro susceptibility to rhinovirus infection is greater for bronchial than for nasal airway epithelial cells in human subjects. J Allergy Clin Immunol 123(6): 1384 1390.
133. Mosser AG, Schneider RA, Amineva SP, Burchell L, Sedgwick JB, Busse WW,, and Gern JE. 2002. Similar frequency of rhinovirus-infectable cells in upper and lower airway epithelium. J Infect Dis 185: 734 743.
134. Gern JE, Galagan DM, Jarjour NN, Dick EC, Busse WW . 1997. Detection of rhinovirus RNA in lower airway cells during experimentally induced infection. Am J Respir Crit Care Med 155 : 1159 1161.[PubMed]
135. Simons E, Schroth MK, Gern JE . 2005. Analysis of tracheal secretions for rhinovirus during natural colds. Pediatr Allergy Immunol 16 : 276 278.[PubMed]
136. Chantzi FM, Papadopoulos NG, Bairamis T, Tsiakou M, Bournousouzis N, Constantopoulos AG, Liapi G, Xatzipsalti M, Kafetzis DA . 2006. Human rhinoviruses in otitis media with effusion. Pediatr Allergy Immunol 17 : 514 518.[PubMed]
137. Pitkäranta A, Arruda E, Malmberg H, Hayden FG . 1997. Detection of rhinovirus in sinus brushings of patients with acute community-acquired sinusitis by reverse transcription-PCR. J Clin Microbiol 35 : 1791 1793.[PubMed]
138. DeMore JP, Weisshaar EH, Vrtis RF, Swenson CA, Evans MD, Morin A, Hazel E,, Bork JA, Kakumanu S, Sorkness R,, Busse WW, Gern JE. 2009. Similar colds in subjects with allergic asthma and nonatopic subjects after inoculation with rhinovirus-16. J Allergy Clin Immunol 124(2): 245 252.
139. Gwaltney JM Jr . 1995. Rhinovirus infection of the normal human airway. Am J Respir Crit Care Med 152 : S36 S39.[PubMed]
140. Halperin SA, Eggleston PA, Hendley JO, Suratt PM, Gröschel DH, Gwaltney JMJ Jr . 1983. Pathogenesis of lower respiratory tract symptoms in experimental rhinovirus infection. Am Rev Respir Dis 128 : 806 810.[PubMed]
141. de Arruda E III, Mifflin TE, Gwaltney JMJ Jr, Winther B, Hayden FG . 1991. Localization of rhinovirus replication in vitro with in situ hybridization. J Med Virol 34 : 38 44.[PubMed]
142. Turner RB, Hendley JO, Gwaltney JM Jr . 1982. Shedding of infected ciliated epithelial cells in rhinovirus colds. J Infect Dis 145 : 849 853.[PubMed]
143. Gustafson LM, Proud D, Hendley JO, Hayden FG, , and Gwaltney JM . 1996. Oral prednisone therapy in experimental rhinovirus infections. J Allergy Clin Immunol 97(4): 1009 1014.
144. Gern JE, French DA, Grindle KA, Brockman-Schneider RA, Konno S, Busse WW . 2003. Double-stranded RNA induces the synthesis of specific chemokines by bronchial epithelial cells. Am J Respir Cell Mol Biol 28 : 731 737.[PubMed]
145. Grassmé H, Riehle A, Wilker B, Gulbins E . 2005. Rhinoviruses infect human epithelial cells via ceramide-enriched membrane platforms. J Biol Chem 280 : 26256 26262.[PubMed]
146. Prather AA, Janicki-Deverts D, Hall MH, Cohen S . 2015. Behaviorally assessed sleep and susceptibility to the common cold. Sleep 38 : 1353 1359.[PubMed]
147. Cohen S, Frank E, Doyle WJ, Skoner DP, Rabin BS, Gwaltney JM Jr . 1998. Types of stressors that increase susceptibility to the common cold in healthy adults. Health Psychol 17 : 214 223.[PubMed]
148. Doyle WJ, Casselbrant ML, Li-Korotky HS, Doyle AP, Lo CY, Turner R, Cohen S . 2010. The interleukin 6 -174 C/C genotype predicts greater rhinovirus illness. J Infect Dis 201 : 199 206.[PubMed]
149. Loisel DA, Du G, Ahluwalia TS, Tisler CJ, Evans MD, Myers RA, Gangnon RE, Moller EK, Bonnelykke K, Bisgaard H, Jackson DJ, Lemanske RF Jr, Nicolae DL, Gern JE, Ober C . 2016. Genetic associations with viral respiratory illnesses and asthma control in children. Clin Exp Allergy 46 : 112 124.[PubMed]
150. Gern JE, Vrtis R, Grindle KA, Swenson C, Busse WW. 2000. Relationship of upper and lower airway cytokines to outcome of experimental rhinovirus infection. Am J Crit Care Med 162: 2226 2231.
151. Becker TM, Durrani SR, Bochkov YA, Devries MK, Rajamanickam V, Jackson DJ . 2013. Effect of exogenous interferons on rhinovirus replication and airway inflammatory responses. Ann Allergy Asthma Immunol 111 : 397 401.[PubMed]
152. Yuta A, Doyle WJ, Gaumond E, Ali M, Tamarkin L, Baraniuk JN, Van Deusen M, Cohen S, Skoner DP . 1998. Rhinovirus infection induces mucus hypersecretion. Am J Physiol 274 : L1017 L1023.[PubMed]
153. Hall DJ, Bates ME, Guar L, Cronan M, Korpi N, Bertics PJ . 2005. The role of p38 MAPK in rhinovirus-induced monocyte chemoattractant protein-1 production by monocytic-lineage cells. J Immunol 174 : 8056 8063.[PubMed]
154. Wang X, Lau C, Wiehler S, Pow A, Mazzulli T, Gutierrez C, Proud D, Chow CW . 2006. Syk is downstream of intercellular adhesion molecule-1 and mediates human rhinovirus activation of p38 MAPK in airway epithelial cells. J Immunol 177 : 6859 6870.[PubMed]
155. Slater L, Bartlett NW, Haas JJ, Zhu J, Message SD, Walton RP, Sykes A, Dahdaleh S, Clarke DL, Belvisi MG, Kon OM, Fujita T, Jeffery PK, Johnston SL, Edwards MR . 2010. Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium. PLoS Pathog 6 : e1001178.[PubMed]
156. Wang Q, Nagarkar DR, Bowman ER, Schneider D, Gosangi B, Lei J, Zhao Y, McHenry CL, Burgens RV, Miller DJ, Sajjan U, Hershenson MB . 2009. Role of double-stranded RNA pattern recognition receptors in rhinovirus-induced airway epithelial cell responses. J Immunol 183 : 6989 6997.[PubMed]
157. Kim J, Sanders SP, Siekierski ES, Casolaro V, Proud D . 2000. Role of NF-kappa B in cytokine production induced from human airway epithelial cells by rhinovirus infection. J Immunol 165 : 3384 3392.[PubMed]
158. Bochkov YA, Hanson KM, Keles S, Brockman-Schneider RA, Jarjour NN, Gern JE . 2010. Rhinovirus-induced modulation of gene expression in bronchial epithelial cells from subjects with asthma. Mucosal Immunol 3 : 69 80.[PubMed]
159. Gavala ML, Bertics PJ, Gern JE . 2011. Rhinoviruses, allergic inflammation, and asthma. Immunol Rev 242 : 69 90.[PubMed]
160. Nakagome K, Bochkov YA, Ashraf S, Brockman-Schneider RA, Evans MD, Pasic TR, Gern JE . 2014. Effects of rhinovirus species on viral replication and cytokine production. J Allergy Clin Immunol 134 : 332 341.[PubMed]
161. Bizzintino J, Lee WM, Laing IA, Vang F, Pappas T, Zhang G, Martin AC, Khoo SK, Cox DW, Geelhoed GC, McMinn PC, Goldblatt J, Gern JE, Le Souëf PN . 2011. Association between human rhinovirus C and severity of acute asthma in children. Eur Respir J 37 : 1037 1042.[PubMed]
162. Kloepfer KM, Lee WM, Pappas TE, Kang TJ, Vrtis RF, Evans MD, Gangnon RE, Bochkov YA, Jackson DJ,, Lemanske RF Jr, Ger n JE . 2014. Detection of pathogenic bacteria during rhinovirus infection is associated with increased respiratory symptoms and asthma exacerbations. J Allergy Clin Immunol 133(5) : 1301 1307.