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

Abstract

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....

Toward Genetics-Based Virus Taxonomy: Comparative Analysis of a Genetics-Based Classification and the Taxonomy of Picornaviruses

“…Specifics of both HRV-C evolution and the two classification frameworks could play a role. The genetic diversity of these viruses in capsid (1A, also known as VP4, and 1D proteins) and nonstructural (3D) regions was previously reported to exceed those of other rhinoviruses (51,69). In the 1D protein, this difference is smallest, and the entire HRV-C diversity was considered to be below the species divergence limit, paving the way for the recognition of HRV-C as a single species.…”

Spread of different rhinovirus B genotypes in hospitalized children in Spain

“… 6 and Simmonds et al. , 4 novel HRVs may be classified following these criteria. In case of HRV‐B species, the pairwise distance, based on partial VP4‐/VP2‐coding region, falls to a minimum value of 10%.…”

Rhinovirus vaccination: the case against

“…Species C variants have not been cultured and, therefore, cannot as yet be formally assigned into separate serotypes. However, sequence data has revealed a large number of distinct genetic lineages identifiable by sequence comparisons in the VP1 and VP4/VP2 gene regions [31]. If these sequence variations correspond to major antigenic differences and different serotypes of rhinovirus C, the range of rhinovirus serotypes may be even wider than was previously thought.…”