title: Analysis of genetic diversity and sites of recombination in human rhinovirus species C.
abstract: 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.
authors.affiliation: Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK.
authors.forename: Chloe L
authors.initials: CL
authors.lastname: McIntyre
authors.forename: E Carol
authors.initials: EC
authors.lastname: McWilliam Leitch
authors.forename: Carita
authors.initials: C
authors.lastname: Savolainen-Kopra
authors.forename: Tapani
authors.initials: T
authors.lastname: Hovi
authors.forename: Peter
authors.initials: P
authors.lastname: Simmonds
mesh_terms: D020121:5' Untranslated Regions; D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000235:genetics; D002874:Chromosome Mapping; D019143:Evolution, Molecular; D005814:Genes, Viral; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D010850:Picornaviridae Infections / Q000821:virology; D011995:Recombination, Genetic; D012229:Rhinovirus / Q000145:classification* / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D036022:Capsid Proteins; C442544:VP2 protein, Rhinovirus; D014764:Viral Proteins; C074995:viral protein 1, rhinovirus