title: Distinguishing molecular features and clinical characteristics of a putative new rhinovirus species, human rhinovirus C (HRV C).
abstract: BACKGROUND
  Human rhinoviruses (HRVs) are the most frequently detected pathogens in acute respiratory tract infections (ARTIs) and yet little is known about the prevalence, recurrence, structure and clinical impact of individual members. During 2007, the complete coding sequences of six previously unknown and highly divergent HRV strains were reported. To catalogue the molecular and clinical features distinguishing the divergent HRV strains, we undertook, for the first time, in silico analyses of all available polyprotein sequences and performed retrospective reviews of the medical records of cases in which variants of the prototype strain, HRV-QPM, had been detected.
  
  
  RESULTS
  Genomic analyses revealed that the six divergent strains, residing within a clade we previously called HRV A2, had the shortest polyprotein of all picornaviruses investigated. Structure-based amino acid alignments identified conserved motifs shared among members of the genus Rhinovirus as well as substantive deletions and insertions unique to the divergent strains. Deletions mostly affected regions encoding proteins traditionally involved in antigenicity and serving as HRV and HEV receptor footprints. Because the HRV A2 strains cannot yet be cultured, we created homology models of predicted HRV-QPM structural proteins. In silico comparisons confirmed that HRV-QPM was most closely related to the major group HRVs. HRV-QPM was most frequently detected in infants with expiratory wheezing or persistent cough who had been admitted to hospital and required supplemental oxygen. It was the only virus detected in 65% of positive individuals. These observations contributed to an objective clinical impact ranging from mild to severe.
  
  
  CONCLUSIONS
  The divergent strains did not meet classification requirements for any existing species of the genus Rhinovirus or Enterovirus. HRV A2 strains should be partitioned into at least one new species, putatively called Human rhinovirus C, populated by members detected with high frequency, from individuals with respiratory symptoms requiring hospital admission.
authors.affiliation: Queensland Paediatric Infectious Diseases Laboratory, Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, Queensland, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: McErlean
authors.forename: Laura A
authors.initials: LA
authors.lastname: Shackelton
authors.forename: Emily
authors.initials: E
authors.lastname: Andrews
authors.forename: Dale R
authors.initials: DR
authors.lastname: Webster
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Lambert
authors.forename: Michael D
authors.initials: MD
authors.lastname: Nissen
authors.forename: Theo P
authors.initials: TP
authors.lastname: Sloots
authors.forename: Ian M
authors.initials: IM
authors.lastname: Mackay
mesh_terms: D020816:Amino Acid Motifs; D004770:Enterovirus / Q000235:genetics; D016679:Genome, Viral; D023281:Genomics; D008968:Molecular Conformation; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012229:Rhinovirus / Q000145:classification* / Q000235:genetics*; D013045:Species Specificity; D014764:Viral Proteins / Q000737:chemistry; D014773:Virology / Q000379:methods
chemical_list: D014764:Viral Proteins