title: Infection and propagation of human rhinovirus C in human airway epithelial cells.
abstract: Human rhinovirus species C (HRV-C) was recently discovered using molecular diagnostic techniques and is associated with lower respiratory tract disease, particularly in children. HRV-C cannot be propagated in immortalized cell lines, and currently sinus organ culture is the only system described that is permissive to HRV-C infection ex vivo. However, the utility of organ culture for studying HRV-C biology is limited. Here, we report that a previously described HRV-C derived from an infectious cDNA, HRV-C15, infects and propagates in fully differentiated human airway epithelial cells but not in undifferentiated cells. We demonstrate that this differentiated epithelial cell culture system supports infection and replication of a second virus generated from a cDNA clone, HRV-C11. We show that HRV-C15 virions preferentially bind fully differentiated airway epithelial cells, suggesting that the block to replication in undifferentiated cells is at the step of viral entry. Consistent with previous reports, HRV-C15 utilizes a cellular receptor other than ICAM-1 or LDLR for infection of differentiated epithelial cells. Furthermore, we demonstrate that HRV-C15 replication can be inhibited by an HRV 3C protease inhibitor (rupintrivir) but not an HRV capsid inhibitor previously under clinical development (pleconaril). The HRV-C cell culture system described here provides a powerful tool for studying the biology of HRV-C and the discovery and development of HRV-C inhibitors.
authors.affiliation: Department of Infectious Diseases and Vaccines, MedImmune LLC, Gaithersburg, Maryland, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Hao
authors.forename: Katie
authors.initials: K
authors.lastname: Bernard
authors.forename: Nita
authors.initials: N
authors.lastname: Patel
authors.forename: Nancy
authors.initials: N
authors.lastname: Ulbrandt
authors.forename: Hui
authors.initials: H
authors.lastname: Feng
authors.forename: Catherine
authors.initials: C
authors.lastname: Svabek
authors.forename: Susan
authors.initials: S
authors.lastname: Wilson
authors.forename: Christina
authors.initials: C
authors.lastname: Stracener
authors.forename: Kathy
authors.initials: K
authors.lastname: Wang
authors.forename: Joann
authors.initials: J
authors.lastname: Suzich
authors.forename: Wade
authors.initials: W
authors.lastname: Blair
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D001483:Base Sequence; D001980:Bronchi / Q000166:cytology / Q000821:virology*; D002454:Cell Differentiation; D017931:DNA Primers; D004847:Epithelial Cells / Q000821:virology; D006367:HeLa Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D010850:Picornaviridae Infections / Q000473:pathology / Q000821:virology*; D016133:Polymerase Chain Reaction; D012229:Rhinovirus / Q000502:physiology*; D014779:Virus Replication
chemical_list: D017931:DNA Primers