title: Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. yabochkov@wisc.edu
authors.forename: Yury A
authors.initials: YA
authors.lastname: Bochkov
authors.forename: Ann C
authors.initials: AC
authors.lastname: Palmenberg
authors.forename: Wai-Ming
authors.initials: WM
authors.lastname: Lee
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Rathe
authors.forename: Svetlana P
authors.initials: SP
authors.lastname: Amineva
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Pasic
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Jarjour
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Liggett
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
mesh_terms: D001483:Base Sequence; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000235:genetics; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D009924:Organ Culture Techniques; D010256:Paranasal Sinuses / Q000821:virology; D010802:Phylogeny; D011973:Receptors, LDL / Q000502:physiology; D011991:Receptors, Virus / Q000502:physiology; D012229:Rhinovirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D013045:Species Specificity; D053585:Virus Attachment
chemical_list: D004279:DNA, Viral; D011973:Receptors, LDL; D011991:Receptors, Virus; D018799:Intercellular Adhesion Molecule-1