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Replication of herpes simplex virus 1 depends on the gamma 134.5 functions that facilitate virus response to interferon and egress in the different stages of productive infection.

Abstract：

:The ability of the gamma(1)34.5 protein to suppress the PKR response plays a crucial role in herpes simplex virus pathogenesis. In this process, the gamma(1)34.5 protein associates with protein phosphatase 1 to form a large complex that dephosphorylates eIF-2alpha and thereby prevents translation shutoff mediated by PKR. Accordingly, gamma(1)34.5 null mutants are virulent in PKR-knockout mice but not in wild-type mice. However, gamma(1)34.5 deletion mutants, with an extragenic compensatory mutation, inhibit PKR activity but remain avirulent, suggesting that the gamma(1)34.5 protein has additional functions. Here, we show that a substitution of the gamma(1)34.5 gene with the NS1 gene from influenza A virus renders viral resistance to interferon involving PKR. The virus replicates as efficiently as wild-type virus in SK-N-SH and CV-1 cells. However, in mouse 3T6 cells, the virus expressing the NS1 protein grows at an intermediate level between the wild-type virus and the gamma(1)34.5 deletion mutant. This decrease in growth, compared to that of the wild-type virus, is due not to an inhibition of viral protein synthesis but rather to a block in virus release or egress. Virus particles are predominantly present in the nucleus and cytoplasm. Notably, deletions in the amino terminus of the gamma(1)34.5 protein lead to a significant decrease in virus growth in mouse 3T6 cells, which is independent of eIF-2alpha dephosphorylation. In correlation, a series of deletions in the amino-terminal domain impair nuclear as well as cytoplasmic egress. These results indicate that efficient viral replication depends on the gamma(1)34.5 functions required to prevent the PKR response and to facilitate virus egress in the different stages during virus infection.

journal_name

J Virol

journal_title

Journal of virology

authors

Jing X,Cerveny M,Yang K,He B

doi

10.1128/JVI.78.14.7653-7666.2004

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

7653-66

issue

eissn

0022-538X

issn

1098-5514

pii

78/14/7653

journal_volume

pub_type

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Replication of herpes simplex virus 1 depends on the gamma 134.5 functions that facilitate virus response to interferon and egress in the different stages of productive infection.