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

Journal of Virology
Xianghong JingBin He

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 c...Continue Reading

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Citations

Nov 18, 2008·The Journal of Biological Chemistry·Dustin VerpootenBin He
Sep 1, 2009·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Cyril X GeorgeCharles E Samuel
Feb 22, 2012·Journal of Virology·Ryuichi KanaiSamuel D Rabkin
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Nov 17, 2016·Scientific Reports·Issac Horng Khit TooSylvie Alonso
Mar 28, 2008·Journal of Virology·Tracy Jo PasiekaDavid A Leib
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Aug 11, 2021·Viruses·Chase KangasBin He
Feb 11, 2012·Trends in Immunology·Ben X Wang, Eleanor N Fish

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