title: Genetics, recombination and clinical features of human rhinovirus species C (HRV-C) infections; interactions of HRV-C with other respiratory viruses.
abstract: To estimate the frequency, molecular epidemiological and clinical associations of infection with the newly described species C variants of human rhinoviruses (HRV), 3243 diagnostic respiratory samples referred for diagnostic testing in Edinburgh were screened using a VP4-encoding region-based selective polymerase chain reaction (PCR) for HRV-C along with parallel PCR testing for 13 other respiratory viruses. HRV-C was the third most frequently detected behind respiratory syncytial virus (RSV) and adenovirus, with 141 infection episodes detected among 1885 subjects over 13 months (7.5%). Infections predominantly targeted the very young (median age 6-12 months; 80% of infections in those <2 years), occurred throughout the year but with peak incidence in early winter months. HRV-C was detected significantly more frequently among subjects with lower (LRT) and upper respiratory tract (URT) disease than controls without respiratory symptoms; HRV-C mono-infections were the second most frequently detected virus (behind RSV) in both disease presentations (6.9% and 7.8% of all cases respectively). HRV variants were classified by VP4/VP2 sequencing into 39 genotypically defined types, increasing the current total worldwide to 60. Through sequence comparisons of the 5'untranslated region (5'UTR), the majority grouped with species A (n = 96; 68%, described as HRV-Ca), the remainder forming a phylogenetically distinct 5'UTR group (HRV-Cc). Multiple and bidirectional recombination events between HRV-Ca and HRV-Cc variants and with HRV species A represents the most parsimonious explanation for their interspersed phylogeny relationships in the VP4/VP2-encoding region. No difference in age distribution, seasonality or disease associations was identified between HRV-Ca and HRV-Cc variants. HRV-C-infected subjects showed markedly reduced detection frequencies of RSV and other respiratory viruses, providing evidence for a major interfering effect of HRV-C on susceptibility to other respiratory virus infections. HRV-C's disease associations, its prevalence and evidence for interfering effects on other respiratory viruses mandates incorporation of rhinoviruses into future diagnostic virology screening.
authors.affiliation: Centre for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Wisdom
authors.forename: Aldona E
authors.initials: AE
authors.lastname: Kutkowska
authors.forename: E Carol
authors.initials: EC
authors.lastname: McWilliam Leitch
authors.forename: Eleanor
authors.initials: E
authors.lastname: Gaunt
authors.forename: Kate
authors.initials: K
authors.lastname: Templeton
authors.forename: Heli
authors.initials: H
authors.lastname: Harvala
authors.forename: Peter
authors.initials: P
authors.lastname: Simmonds
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D010850:Picornaviridae Infections / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D011995:Recombination, Genetic / Q000235:genetics*; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D012141:Respiratory Tract Infections / Q000821:virology; D012229:Rhinovirus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D012621:Seasons; D055815:Young Adult