West Nile virus evades activation of interferon regulatory factor 3 through RIG-I-dependent and -independent pathways without antagonizing host defense signaling.

Abstract:

:The ability of viruses to control and/or evade the host antiviral response is critical to the establishment of a productive infection. We have previously shown that West Nile virus NY (WNV-NY) delays activation of interferon regulatory factor 3 (IRF-3), a transcription factor critical to the initiation of the antiviral response. Here we demonstrate that the delayed activation of IRF-3 is essential for WNV-NY to achieve maximum virus production. Furthermore, WNV-NY utilizes a unique mechanism to control activation of IRF-3. In contrast to many other viruses that impose a nonspecific block to the IRF-3 pathway, WNV-NY eludes detection by the host cell at early times postinfection. To better understand this process, we assessed the role of the pathogen recognition receptor (PRR) retinoic acid-inducible gene I (RIG-I) in sensing WNV-NY infection. RIG-I null mouse embryo fibroblasts (MEFs) retained the ability to respond to WNV-NY infection; however, the onset of the host response was delayed compared to wild-type (WT) MEFs. This suggests that RIG-I is involved in initially sensing WNV-NY infection, while other PRRs sustain and/or amplify the host response later in infection. The delayed initiation of the host response correlated with an increase in WNV-NY replication in RIG-I null MEFs compared to WT MEFs. Our data suggest that activation of the host response by RIG-I early in infection is important for controlling replication of WNV-NY. Furthermore, pathogenic strains of WNV may have evolved to circumvent stimulation of the host response until after replication is well under way.

journal_name

J Virol

journal_title

Journal of virology

authors

Fredericksen BL,Gale M Jr

doi

10.1128/JVI.80.6.2913-2923.2006

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

2913-23

issue

6

eissn

0022-538X

issn

1098-5514

pii

80/6/2913

journal_volume

80

pub_type

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