ArticlePLoS pathogens2011
Granzyme B inhibits vaccinia virus production through proteolytic cleavage of eukaryotic initiation factor 4 gamma 3.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Granzyme B and melittin in cancer immunotherapy: molecular mechanisms and therapeutic perspectives in head and neck cancers.Frontiers in immunology · 2025Review
- Review
- Noncytotoxic functions of killer cell granzymes in viral infections.PLoS pathogens · 2021Review
- Enrichment of CCR6European journal of immunology · 2021Article
- Oxidative and Non-Oxidative Antimicrobial Activities of the Granzymes.Frontiers in immunology · 2021Review
- GATA1/SP1 and miR-874 mediate enterovirus-71-induced apoptosis in a granzyme-B-dependent manner in Jurkat cells.Archives of virology · 2020Article
- Translational control during poxvirus infection.Wiley interdisciplinary reviews. RNA · 2019Review
- Keeping it in check: chronic viral infection and antiviral immunity in the brain.Nature reviews. Neuroscience · 2016Review
- Herpes simplex virus ICP27 regulates alternative pre-mRNA polyadenylation and splicing in a sequence-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Quantitative Proteomic Analysis of Duck Ovarian Follicles Infected with Duck Tembusu Virus by Label-Free LC-MS.Frontiers in microbiology · 2016Article
- Perforin and granzymes: function, dysfunction and human pathology.Nature reviews. Immunology · 2015Review
- The spliceosome factor SART1 exerts its anti-HCV action through mRNA splicing.Journal of hepatology · 2015Article
- Impact of distinct poxvirus infections on the specificities and functionalities of CD4+ T cell responses.Journal of virology · 2014Article
- Germline copy number variations associated with breast cancer susceptibility in a Japanese population.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- Hantavirus-infection confers resistance to cytotoxic lymphocyte-mediated apoptosis.PLoS pathogens · 2013Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Cytotoxic T lymphocytes (CTLs) are the major killer of virus-infected cells. Granzyme B (GrB) from CTLs induces apoptosis in target cells by cleavage and activation of substrates like caspase-3 and Bid. However, while undergoing apoptosis, cells are still capable of producing infectious viruses unless a mechanism exists to specifically inhibit viral production. Using proteomic approaches, we identified a novel GrB target that plays a major role in protein synthesis: eukaryotic initiation factor 4 gamma 3 (eIF4G3). We hypothesized a novel role for GrB in translation of viral proteins by targeting eIF4G3, and showed that GrB cleaves eIF4G3 specifically at the IESD(1408)S sequence. Both GrB and human CTL treatment resulted in degradation of eIF4G3 and reduced rates of translation. When Jurkat cells infected with vaccinia virus were treated with GrB, there was a halt in viral protein synthesis and a decrease in production of infectious new virions. The GrB-induced inhibition of viral translation was independent of the activation of caspases, as inhibition of protein synthesis still occurred with addition of the pan-caspase inhibitor zVAD-fmk. This demonstrated for the first time that GrB prevents the production of infectious vaccinia virus by targeting the host translational machinery.
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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.