Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C

Nat Med. 2011 May;17(5):627-32. doi: 10.1038/nm.2358. Epub 2011 Apr 10.


A recently recognized human rhinovirus species C (HRV-C) is associated with up to half of HRV infections in young children. Here we propagated two HRV-C isolates ex vivo in organ culture of nasal epithelial cells, sequenced a new C15 isolate and developed the first, to our knowledge, reverse genetics system for HRV-C. Using contact points for the known HRV receptors, intercellular adhesion molecule-1 (ICAM-1) and low-density lipoprotein receptor (LDLR), inter- and intraspecies footprint analyses predicted a unique cell attachment site for HRV-Cs. Antibodies directed to binding sites for HRV-A and -B failed to inhibit HRV-C attachment, consistent with the alternative receptor footprint. HRV-A and HRV-B infected HeLa and WisL cells but HRV-C did not. However, HRV-C RNA synthesized in vitro and transfected into both cell types resulted in cytopathic effect and recovery of functional virus, indicating that the viral attachment mechanism is a primary distinguishing feature of HRV-C.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Base Sequence
  • Cytopathogenic Effect, Viral
  • DNA, Viral / genetics
  • Genome, Viral
  • HeLa Cells
  • Humans
  • Intercellular Adhesion Molecule-1 / physiology
  • Organ Culture Techniques
  • Paranasal Sinuses / virology
  • Phylogeny
  • Receptors, LDL / physiology
  • Receptors, Virus / physiology
  • Rhinovirus / classification*
  • Rhinovirus / genetics*
  • Rhinovirus / isolation & purification
  • Rhinovirus / physiology
  • Species Specificity
  • Virus Attachment


  • DNA, Viral
  • Receptors, LDL
  • Receptors, Virus
  • Intercellular Adhesion Molecule-1