Open AccessThe Naturally Attenuated Kunjin Strain of West Nile Virus Shows Enhanced Sensitivity to the Host Type I Interferon Response
Author(s) -
Stephanie Daffis,
Helen M. Lazear,
Wenjun Liu,
Michelle D. Audsley,
Michael J. Engle,
Alexander A. Khromykh,
Michael S. Diamond
Publication year - 2011
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.00232-11
Subject(s) - biology , interferon , virology , west nile virus , strain (injury) , interferon type i , virulence , virus , interferon regulatory factors , host (biology) , flavivirus , microbiology and biotechnology , immunology , immune system , innate immune system , gene , genetics , anatomy
The host determinants that contribute to attenuation of the naturally occurring nonpathogenic strain of West Nile virus (WNV), the Kunjin strain (WNVKUN ), remain unknown. Here, we show that compared to a highly pathogenic North American strain, WNVKUN exhibited an enhanced sensitivity to the antiviral effects of type I interferon. Our studies establish that the virulence of WNVKUN can be restored in cells and mice deficient in specific interferon regulatory factors (IRFs) or the common type I interferon receptor. Thus, WNVKUN is attenuated primarily through its enhanced restriction by type I interferon- and IRF-3-dependent mechanisms.