ArticleThe Journal of biological chemistry2011
ICP34.5 protein of herpes simplex virus facilitates the initiation of protein translation by bridging eukaryotic initiation factor 2alpha (eIF2alpha) and protein phosphatase 1.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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83 citing papers in PubMed, 114 citations in OpenAlex.
- Reprogramming innate immunity through viral interference: A double-edged strategy for enhancing and containing gene therapies.Molecular therapy. Nucleic acids · 2026Review
- Differential Sensitivity of HSV-1 and PRV to IFN-λ Reveals a Neuron-Specific Antiviral Role for RSAD2.bioRxiv : the preprint server for biology · 2026Article
- Glutamine-Linked Cellular Stress Responses in Viral Infection: Mechanisms, Crosstalk, and Future Perspectives.International journal of molecular sciences · 2026Review
- Engineering HSV-1 for oncolytic therapy: From molecular entry mechanisms to retargeting strategies.Genes & diseases · 2026Review
- Design and Efficacy of Oncolytic Viruses and Antitumor Vaccines: A Dead End in the Immunotherapy of Pancreatic Cancer?International journal of molecular sciences · 2025Review
- Co-expression of HSV-1 ICP34.5 enhances the expression of gene delivered by self-amplifying RNA and mitigates its immunogenicity.FEBS open bio · 2025Article
- Inhibition of mitophagy via the EIF2S1-ATF4-PRKN pathway contributes to viral encephalitis.Journal of advanced research · 2025Article
- Multi-Faceted Roles of Stress Granules in Viral Infection.Microorganisms · 2025Review
- AlphaFold models of host-pathogen interactions elucidate the prevalence and structural modes of molecular mimicry.bioRxiv : the preprint server for biology · 2025Article
- Article
- Understanding the interplay between oHSV and the host immune system: Implications for therapeutic oncolytic virus development.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- ADAR1 p150 prevents HSV-1 from triggering PKR/eIF2α-mediated translational arrest and is required for efficient viral replication.PLoS pathogens · 2025Article
- Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets.Frontiers in immunology · 2025Review
- Article
- Protein phosphatase 1 suppresses PKR/EIF2α signaling during human cytomegalovirus infection.Journal of virology · 2024Article
- The NS2B-PP1α-eIF2α axis: Inhibiting stress granule formation and Boosting Zika virus replication.PLoS pathogens · 2024Article
- Personalizing Oncolytic Immunovirotherapy Approaches.Molecular diagnosis & therapy · 2024Article
- Emerging roles of the Protein Phosphatase 1 (PP1) in the context of viral infections.Cell communication and signaling : CCS · 2024Review
- Strategies for engineering oncolytic viruses to enhance cancer immunotherapy.Frontiers in pharmacology · 2024Review
- Advanced progress in the genetic modification of the oncolytic HSV-1 virus.Frontiers in oncology · 2024Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The ICP34.5 protein of herpes simplex virus type 1 is a neurovirulence factor that plays critical roles in viral replication and anti-host responses. One of its functions is to recruit protein phosphatase 1 (PP1) that leads to the dephosphorylation of the α subunit of translation initiation factor eIF2 (eIF2α), which is inactivated by infection-induced phosphorylation. As PP1 is a protein phosphatase with a wide range of substrates, the question remains to be answered how ICP34.5 directs PP1 to specifically dephosphorylate eIF2α. Here we report that ICP34.5 not only binds PP1 but also associates with eIF2α by in vitro and in vivo assays. The binding site of eIF2α is identified at amino acids 233-248 of ICP34.5, which falls in the highly homologous region with human gene growth arrest and DNA damage 34. The interaction between ICP34.5 and eIF2α is independent of the phosphorylation status of eIF2α at serine 51. Deletion mutation of this region results in the failure of dephosphorylation of eIF2α by PP1 and, consequently, interrupts viral protein synthesis and replication. Our data illustrated that the binding between viral protein ICP34.5 and the host eIF2α is crucial for the specific dephosphorylation of eIF2α by PP1. We propose that herpes simplex virus protein ICP34.5 bridges PP1 and eIF2α via their binding motifs and thereby facilitates the protein synthesis and viral replication.
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