Title | Molecular modeling, organ culture and reverse genetics for a newly identified human rhinovirus C. | ||
Author | Bochkov, Yury A; Palmenberg, Ann C; Lee, Wai-Ming; Rathe, Jennifer A; Amineva, Svetlana P; Sun, Xin; Pasic, Thomas R; Jarjour, Nizar N; Liggett, Stephen B; Gern, James E | ||
Journal | Nat Med | Publication Year/Month | 2011-May |
PMID | 21483405 | PMCID | PMC3089712 |
Affiliation | 1.Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. yabochkov@wisc.edu. |
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.