ArticleJournal of virology2009
Increased eIF2alpha phosphorylation attenuates replication of herpes simplex virus 2 vhs mutants in mouse embryonic fibroblasts and correlates with reduced accumulation of the PKR antagonist ICP34.5.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Multi-Faceted Roles of Stress Granules in Viral Infection.Microorganisms · 2025Review
- Coronavirus endoribonuclease nsp15 suppresses host protein synthesis and evades PKR-eIF2α-mediated translation shutoff to ensure viral protein synthesis.PLoS pathogens · 2025Article
- ER stress induces caspase-2-tBID-GSDME-dependent cell death in neurons lytically infected with herpes simplex virus type 2.The EMBO journal · 2023Article
- ICP8-vhs- HSV-2 Vaccine Expressing B7 Costimulation Molecules Optimizes Safety and Efficacy against HSV-2 Infection in Mice.Viruses · 2023Article
- An upward 9.4 T static magnetic field inhibits DNA synthesis and increases ROS-P53 to suppress lung cancer growth.Translational oncology · 2021Article
- "Non-Essential" Proteins of HSV-1 with Essential Roles In Vivo: A Comprehensive Review.Viruses · 2020Review
- Oncolytic Virus Encoding a Master Pro-Inflammatory Cytokine Interleukin 12 in Cancer Immunotherapy.Cells · 2020Review
- The Interplay of Viral and Host Factors in Chikungunya Virus Infection: Targets for Antiviral Strategies.Viruses · 2018Review
- The Herpes Simplex Virus Virion Host Shutoff Protein Enhances Translation of Viral True Late mRNAs Independently of Suppressing Protein Kinase R and Stress Granule Formation.Journal of virology · 2016Article
- Neurons versus herpes simplex virus: the innate immune interactions that contribute to a host-pathogen standoff.Future virology · 2015Article
- Knockdown of elF3a inhibits collagen synthesis in renal fibroblasts via Inhibition of transforming growth factor-β1/Smad signaling pathway.International journal of clinical and experimental pathology · 2015Article
- The herpes simplex virus 2 virion-associated ribonuclease vhs interferes with stress granule formation.Journal of virology · 2014Article
- Up to four distinct polypeptides are produced from the γ34.5 open reading frame of herpes simplex virus 2.Journal of virology · 2014Article
- mRNA decay during herpes simplex virus (HSV) infections: mutations that affect translation of an mRNA influence the sites at which it is cleaved by the HSV virion host shutoff (Vhs) protein.Journal of virology · 2013Article
- The herpes simplex virus 1 vhs protein enhances translation of viral true late mRNAs and virus production in a cell type-dependent manner.Journal of virology · 2011Article
- The virion host shutoff endonuclease (UL41) of herpes simplex virus interacts with the cellular cap-binding complex eIF4F.Journal of virology · 2010Article
- Evidence for translational regulation by the herpes simplex virus virion host shutoff protein.Journal of virology · 2010Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Herpes simplex virus 2 (HSV-2) strains containing mutations in the virion host shutoff (vhs) protein are attenuated for replication compared with wild-type virus in mouse embryonic fibroblasts (MEFs). However, HSV-2 vhs mutants replicate to near wild-type levels in the absence of the RNA-activated protein kinase (PKR). PKR is one of several kinases that phosphorylates the eukaryotic initiation factor 2alpha (eIF2alpha) to inhibit translation initiation, and we previously found that more of the phosphorylated form of eIF2alpha accumulates in MEFs infected with HSV-2 vhs mutants than with wild-type virus. Here, we show that this increase in phosphorylated eIF2alpha is primarily PKR dependent. Using MEFs expressing nonphosphorylatable eIF2alpha, we demonstrate that phosphorylated eIF2alpha is the primary cause of attenuated replication of HSV-2 vhs mutants and that attenuation correlates with decreased accumulation of viral proteins. Normally, HSV antagonizes eIF2alpha phosphorylation through the action of ICP34.5, which redirects protein phosphatase 1alpha (PP1alpha) to dephosphorylate eIF2alpha during infection. We show that ICP34.5 does not accumulate efficiently in MEFs infected with HSV-2 vhs mutant viruses, suggesting that the accumulation of phosphorylated eIF2alpha and the attenuated phenotype of HSV-2 vhs mutants in MEFs result from a deficiency in ICP34.5.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.