Genetics, Recombination and Clinical Features of Human Rhinovirus Species C (HRV-C) Infections; Interactions of HRV-C with Other Respiratory Viruses

Wisdom, Anne; Kutkowska, Aldona E.; Leitch, E. Carol McWilliam; Gaunt, Eleanor; Templeton, Kate; Harvala, Heli; Simmonds, Peter

doi:10.1371/journal.pone.0008518

Cited by 69 publications

(78 citation statements)

References 46 publications

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“…In our study, all 67 HRV-C strains possessed sequences already reported in GenBank, as of 30 April 2010. In addition, while recombination events are known to be frequent among HEVs (15), analysis of the 5Ј NCR of HRVs is consistent with multiple interspecies recombination events also in HRV evolution (22).…”

supporting

confidence: 53%

“…However, to date, HRV-C strains are not taxonomically classified into types, even though a similar level of molecular diversity (equal or greater than HRV-A and HRV-B) seems to exist among HRV-C strains or variants. Using a 10% nucleotide divergence as a threshold, in October 2009, 47 hypothetical HRV-C types were identified (23), and in December 2009 the number of potential types grew to 60 (22). In our study, all 67 HRV-C strains possessed sequences already reported in GenBank, as of 30 April 2010.…”

mentioning

confidence: 52%

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Phylogenetic Patterns of Human Respiratory Picornavirus Species, Including the Newly Identified Group C Rhinoviruses, during a 1-Year Surveillance of a Hospitalized Patient Population in Italy

2011

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supporting

confidence: 53%

mentioning

confidence: 52%

Phylogenetic Patterns of Human Respiratory Picornavirus Species, Including the Newly Identified Group C Rhinoviruses, during a 1-Year Surveillance of a Hospitalized Patient Population in Italy

2011

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“…In addition, HRV-associated wheezing in infancy is predictive of the development of childhood asthma (17). Previous reports suggested that HRV-C is associated with more severe illness than HRV-A or HRV-B (19,32,43,47). More recent studies show that HRV-A as well as HRV-C are the most prevalent HRVs identified in hospitalized children (7,27,37,41,49), while HRV-C infection is associated with an increase in hospitalization events in atopic children (4).…”

mentioning

confidence: 99%

Infection and Propagation of Human Rhinovirus C in Human Airway Epithelial Cells

Hao¹,

Bernard²,

Patel³

et al. 2012

J Virol

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Human rhinovirus species C (HRV-C) was recently discovered using molecular diagnostic techniques and is associated with lower respiratory tract disease, particularly in children. HRV-C cannot be propagated in immortalized cell lines, and currently sinus organ culture is the only system described that is permissive to HRV-C infection ex vivo. However, the utility of organ culture for studying HRV-C biology is limited. Here, we report that a previously described HRV-C derived from an infectious cDNA, HRV-C15, infects and propagates in fully differentiated human airway epithelial cells but not in undifferentiated cells. We demonstrate that this differentiated epithelial cell culture system supports infection and replication of a second virus generated from a cDNA clone, HRV-C11. We show that HRV-C15 virions preferentially bind fully differentiated airway epithelial cells, suggesting that the block to replication in undifferentiated cells is at the step of viral entry. Consistent with previous reports, HRV-C15 utilizes a cellular receptor other than ICAM-1 or LDLR for infection of differentiated epithelial cells. Furthermore, we demonstrate that HRV-C15 replication can be inhibited by an HRV 3C protease inhibitor (rupintrivir) but not an HRV capsid inhibitor previously under clinical development (pleconaril). The HRV-C cell culture system described here provides a powerful tool for studying the biology of HRV-C and the discovery and development of HRV-C inhibitors.

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“…Genetic characterization of HRV-C amplified from clinical specimens has provided evidence for extensive heterogeneity in the VP4/VP2 region, the existence of two phylogenetically separate groups of sequences in the 59-UTR (one resembling sequences found in species A rhinoviruses; Han et al, 2009;Huang et al, 2009;Savolainen-Kopra et al, 2009b;Wisdom et al, 2009a) and substantial sequence divergence throughout the genome of the 11 full-length HRV-C sequences obtained to date (Lamson et al, 2006;Lau et al, 2007;Kistler et al, 2007;McErlean et al, 2007;Huang et al, 2009;Tapparel et al, 2009b;Arden et al, 2010b). Although we currently lack the means to classify HRV-C serologically (as has been achieved for other rhinovirus and enterovirus species), we recognize and are responding to the need to develop a classification system for this species.…”

Section: Proposal Aimsmentioning

confidence: 99%

“…However, several phylogeny violations occurred between the 59-UTR and VP4/VP2 trees, originating from a series of likely interspecies recombination events with breakpoints towards the 39 end of the 59-UTR (Han et al, 2009;Huang et al, 2009;Savolainen-Kopra et al, 2009b;Wisdom et al, 2009a).…”

Section: Rhinovirus Recombinationmentioning

confidence: 99%

Proposals for the classification of human rhinovirus species C into genotypically assigned types

Simmonds

McIntyre

Savolainen-Kopra

et al. 2010

Journal of General Virology

211

163

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Human rhinoviruses (HRVs) are common respiratory pathogens associated with mild upper respiratory tract infections, but also increasingly recognized in the aetiology of severe lower respiratory tract disease. Wider use of molecular diagnostics has led to a recent reappraisal of HRV genetic diversity, including the discovery of HRV species C (HRV-C), which is refractory to traditional virus isolation procedures. Although it is heterogeneous genetically, there has to date been no attempt to classify HRV-C into types analogous to the multiple serotypes identified for HRV-A and -B and among human enteroviruses. Direct investigation of cross-neutralization properties of HRV-C is precluded by the lack of methods for in vitro culture, but sequences from the capsid genes (VP1 and partial VP4/VP2) show evidence for marked phylogenetic clustering, suggesting the possibility of a genetically based system comparable to that used for the assignment of new enterovirus types. We propose a threshold of 13 % divergence for VP1 nucleotide sequences for type assignment, a level that classifies the current dataset of 86 HRV-C VP1 sequences into a total of 33 types. We recognize, however, that most HRV-C sequence data have been collected in the VP4/VP2 region (currently 701 sequences between positions 615 and 1043). We propose a subsidiary classification of variants showing .10 % divergence in VP4/ VP2, but lacking VP1 sequences, to 28 provisionally assigned types (subject to confirmation once VP1 sequences are determined). These proposals will assist in future epidemiological and clinical studies of HRV-C conducted by different groups worldwide, and provide the foundation for future exploration of type-associated differences in clinical presentations and biological properties. IntroductionHuman rhinoviruses (HRVs) are highly prevalent respiratory pathogens, most commonly associated with mild upper respiratory tract disease and exacerbations of preexisting respiratory disease such as asthma. They are also increasingly recognized as underlying more severe disease manifestations, such as bronchiolitis in young children and in the immunosuppressed. The increasing use of molecular methods for respiratory virus screening has contributed to this reappraisal of rhinoviruses, as has the recent discovery of an entirely novel rhinovirus group, refractory to previously used virus isolation methods but now known to be highly prevalent and widely circulating worldwide (Arden et al., 2006;Kaiser et al., 2006;Lamson et al., 2006;Kistler et al., 2007;Lau et al., 2007;Lee et al., 2007;McErlean et al., 2007;Renwick et al., 2007;Olenec et al., 2010).These newly characterized rhinoviruses have been proposed to belong to a novel species of rhinovirus (designated species C; HRV-C), recognizing their substantial sequence divergence from other classified species within the genus Enterovirus of picornaviruses (Carstens, 2010;Knowles, 2010) (Fig. 1a). Clinically and biologically, they share many attributes with the other designated HRV species, HRV-A and -B....

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Genetics, Recombination and Clinical Features of Human Rhinovirus Species C (HRV-C) Infections; Interactions of HRV-C with Other Respiratory Viruses

Cited by 69 publications

References 46 publications

Phylogenetic Patterns of Human Respiratory Picornavirus Species, Including the Newly Identified Group C Rhinoviruses, during a 1-Year Surveillance of a Hospitalized Patient Population in Italy

Phylogenetic Patterns of Human Respiratory Picornavirus Species, Including the Newly Identified Group C Rhinoviruses, during a 1-Year Surveillance of a Hospitalized Patient Population in Italy

Infection and Propagation of Human Rhinovirus C in Human Airway Epithelial Cells

Proposals for the classification of human rhinovirus species C into genotypically assigned types

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