title: A diverse group of previously unrecognized human rhinoviruses are common causes of respiratory illnesses in infants.
abstract: BACKGROUND
  Human rhinoviruses (HRVs) are the most prevalent human pathogens, and consist of 101 serotypes that are classified into groups A and B according to sequence variations. HRV infections cause a wide spectrum of clinical outcomes ranging from asymptomatic infection to severe lower respiratory symptoms. Defining the role of specific strains in various HRV illnesses has been difficult because traditional serology, which requires viral culture and neutralization tests using 101 serotype-specific antisera, is insensitive and laborious.
  
  
  RESULTS
  To directly type HRVs in nasal secretions of infants with frequent respiratory illnesses, we developed a sensitive molecular typing assay based on phylogenetic comparisons of a 260-bp variable sequence in the 5' noncoding region with homologous sequences of the 101 known serotypes. Nasal samples from 26 infants were first tested with a multiplex PCR assay for respiratory viruses, and HRV was the most common virus found (108 of 181 samples). Typing was completed for 101 samples and 103 HRVs were identified. Surprisingly, 54 (52.4%) HRVs did not match any of the known serotypes and had 12-35% nucleotide divergence from the nearest reference HRVs. Of these novel viruses, 9 strains (17 HRVs) segregated from HRVA, HRVB and human enterovirus into a distinct genetic group ("C"). None of these new strains could be cultured in traditional cell lines.
  
  
  CONCLUSIONS
  By molecular analysis, over 50% of HRV detected in sick infants were previously unrecognized strains, including 9 strains that may represent a new HRV group. These findings indicate that the number of HRV strains is considerably larger than the 101 serotypes identified with traditional diagnostic techniques, and provide evidence of a new HRV group.
authors.affiliation: Department of Pediatrics and Medicine, University of Wisconsin, Madison, Wisconsin, United States of America. wlee5@wisc.edu
authors.forename: Wai-Ming
authors.initials: WM
authors.lastname: Lee
authors.forename: Christin
authors.initials: C
authors.lastname: Kiesner
authors.forename: Tressa
authors.initials: T
authors.lastname: Pappas
authors.forename: Iris
authors.initials: I
authors.lastname: Lee
authors.forename: Kris
authors.initials: K
authors.lastname: Grindle
authors.forename: Tuomas
authors.initials: T
authors.lastname: Jartti
authors.forename: Bogdan
authors.initials: B
authors.lastname: Jakiela
authors.forename: Robert F
authors.initials: RF
authors.lastname: Lemanske
authors.forename: Peter A
authors.initials: PA
authors.lastname: Shult
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
mesh_terms: D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005814:Genes, Viral; D016679:Genome, Viral; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D010850:Picornaviridae Infections / Q000235:genetics* / Q000821:virology*; D012141:Respiratory Tract Infections / Q000235:genetics* / Q000821:virology*; D012229:Rhinovirus / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: D018076:DNA, Complementary