Herpes simplex virus 1 has multiple mechanisms for blocking virus-induced interferon production.

Abstract:

:In response to viral infection, host cells elicit a number of responses, including the expression of alpha/beta interferon (IFN-alpha/beta). In these cells, IFN regulatory factor-3 (IRF-3) undergoes a sequence of posttranslational modifications that allow it to act as a potent transcriptional coactivator of specific IFN genes, including IFN-beta. We investigated the mechanisms by which herpes simplex virus 1 (HSV-1) inhibits the production of IFN-beta mediated by the IRF-3 signaling pathway. Here, we show that HSV-1 infection can block the accumulation of IFN-beta triggered by Sendai virus (SeV) infection. Our results indicate that HSV-1 infection blocks the nuclear accumulation of activated IRF-3 but does not block the initial virus-induced phosphorylation of IRF-3. The former effect was at least partly mediated by increased turnover of IRF-3 in HSV-1-infected cells. Using mutant viruses, we determined that the immediate-early protein ICP0 was necessary for the inhibition of IRF-3 nuclear accumulation. Expression of ICP0 also had the ability to reduce IFN-beta production induced by SeV infection. ICP0 has been shown previously to play a role in HSV-1 sensitivity to IFN and in the inhibition of antiviral gene production. However, we observed that an ICP0 mutant virus still retained the ability to inhibit the production of IFN-beta. These results argue that HSV-1 has multiple mechanisms to inhibit the production of IFN-beta, providing additional ways in which HSV-1 can block the IFN-mediated host response.

journal_name

J Virol

journal_title

Journal of virology

authors

Melroe GT,DeLuca NA,Knipe DM

doi

10.1128/JVI.78.16.8411-8420.2004

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

8411-20

issue

16

eissn

0022-538X

issn

1098-5514

pii

78/16/8411

journal_volume

78

pub_type

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