A collaborative report: Rhinoviruses—Extension of the numbering system

Journal of General Virology

et al. 2010

209

163

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....

Section: Classification Of Enteroviruses and Rhinoviruses Into Serotypesmentioning

confidence: 99%

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

Simmonds

McIntyre

Journal of General Virology

et al. 2010

209

163

“…HRV encompasses 100 designated serotypes, including two antigenically distinct subtypes of serotype HRV1 (HRV1A and HRV1B) (Hamparian et al, 1987;Kapikian et al, 1967Kapikian et al, , 1971. The current taxonomy is based on genetic relationships of HRV.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of human rhinovirus field strains isolated during surveillance of enteroviruses

Blomqvist

Journal of General Virology

Paananen

et al. 2009

Human rhinoviruses (HRVs), which are the most frequent causative agents of acute upper respiratory tract infections, are abundant worldwide. We have identified HRV strains in environmental specimens collected in Finland, Latvia and Slovakia during the surveillance of polioand other enteroviruses. These acid-sensitive HRV strains were isolated under conditions optimized for growth of most of the enteroviruses, i.e. in stationary human rhabdomyosarcoma cells incubated at 36 6C. Phylogenetic analysis of the sequences derived from the partial 59 noncoding region and the capsid region coding for proteins VP4/VP2 and VP1 showed that the HRV field strains clustered together with prototype strains of the HRV minor receptor group. Partial sequences of the 3D polymerase coding region generally followed this pattern, with the exception of a set of three HRV field strains that formed a subcluster not close to any of the established HRV-A types, suggesting that recombination may have occurred during evolution of these HRV strains. Phylogenetic analysis of the VP4/VP2 capsid protein coding region showed that the 'environmental' HRV field strains were practically identical to HRV strains recently sequenced by others in Australia, the United States and Japan. Analysis of amino acids corresponding to the intercellular adhesion molecule-1 receptor footprint in major receptor group HRVs and also in the low-density lipoprotein receptor footprint of minor receptor group HRVs showed conservation of the 'minor receptor group-like' amino acids, indicating that the field strains may have maintained their minor receptor group specificity. INTRODUCTIONHuman rhinoviruses (HRVs) belong to the family Picornaviridae and together with human enteroviruses (HEV) and a number of non-human enterovirus strains comprise the largest genus (Enterovirus) in the family (Knowles, 2008). Clinical illnesses caused by HRV are typically mild and self-limiting upper respiratory tract infections or common colds, but HRVs have also been increasingly associated with other clinical consequences of respiratory tract infection such as acute otitis media (NoksoKoivisto et al., 2004;Pitkaranta et al., 1998;Vesa et al., 2001), acute community-acquired sinusitis (Pitkaranta et al., 1997(Pitkaranta et al., , 2001), bronchiolitis (Hayden, 2004), pneumonia (Papadopoulos, 2004 and exacerbations of existing respiratory disorders such as asthma (Gern, 2002) and chronic obstructive pulmonary disease (Greenberg, 2002).HRV encompasses 100 designated serotypes, including two antigenically distinct subtypes of serotype HRV1 (HRV1A and HRV1B) (Hamparian et al., 1987;Kapikian et al., 1967Kapikian et al., , 1971. The current taxonomy is based on genetic relationships of HRV. Genetic analysis of VP4/VP2 (Savolainen et al., 2002a) and VP1 (Laine et al., 2005; Ledford et al., 2004) capsid protein coding regions showed that the 100 serotypes cluster into two genetically distinct species, HRV-A and HRV-B. One HRV strain originally assigned as HRV87 belongs to the enterovirus species H...

“…In the case of species A and B, a total of 74 and 25 different serotypes, respectively, have been defined using cross-neutralization assays in cell culture (14,18,19). Available nucleotide sequences from the capsid region of HRV-C reveal similar or even greater diversity than is found between species A and B sero-types, but its lack of culturability currently precludes an equivalent classification of HRV-C into serotypes.…”

mentioning

confidence: 99%

Analysis of Genetic Diversity and Sites of Recombination in Human Rhinovirus Species C

McIntyre

Leitch

et al. 2010

J Virol

102

Human rhinoviruses (HRVs) are a highly prevalent and diverse group of respiratory viruses. Although HRV-A and HRV-B are traditionally detected by virus isolation, a series of unculturable HRV variants have recently been described and assigned as a new species (HRV-C) within the picornavirus Enterovirus genus. To investigate their genetic diversity and occurrence of recombination, we have performed comprehensive phylogenetic analysis of sequences from the 5 untranslated region (5 UTR), VP4/VP2, VP1, and 3Dpol regions amplified from 89 HRV-C-positive respiratory samples and available published sequences. Branching orders of VP4/VP2, VP1, and 3Dpol trees were identical, consistent with the absence of intraspecies recombination in the coding regions. However, numerous tree topology changes were apparent in the 5 UTR, where >60% of analyzed HRV-C variants showed recombination with species A sequences. Two recombination hot spots in stem-loop 5 and the polypyrimidine tract in the 5 UTR were mapped using the program GroupingScan. Available HRV-C sequences showed evidence for additional interspecies recombination with HRV-A in the 2A gene, with breakpoints mapping precisely to the boundaries of the C-terminal domain of the encoded proteinase. Pairwise distances between HRV-C variants in VP1 and VP4/VP2 regions fell into two separate distributions, resembling inter-and intraserotype distances of species A and B. These observations suggest that, without serological cross-neutralization data, HRV-C genetic groups may be equivalently classified into types using divergence thresholds derived from distance distributions. The extensive sequence data from multiple genome regions of HRV-C and analyses of recombination in the current study will assist future formulation of consensus criteria for HRV-C type assignment and identification.