ArticleCell death and differentiation2013
Granzyme M targets host cell hnRNP K that is essential for human cytomegalovirus replication.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Cytotoxic lymphocytes counteract viral type I interferon immune evasion.PLoS pathogens · 2026Article
- Human cytomegalovirus UL78 is a nuclear-localized GPCR necessary for efficient reactivation from latent infection in CD34Journal of virology · 2025Article
- The CXCL8/MAPK/hnRNP-K axis enables susceptibility to infection by EV-D68, rhinovirus, and influenza virus in vitro.Nature communications · 2025Article
- Article
- Natural killer cells induce HIV-1 latency reversal after treatment with pan-caspase inhibitors.Frontiers in immunology · 2022Article
- Noncytotoxic functions of killer cell granzymes in viral infections.PLoS pathogens · 2021Review
- Intracellular and Extracellular Roles of Granzyme K.Frontiers in immunology · 2021Review
- CAR-T cells leave the comfort zone: current and future applications beyond cancer.Immunotherapy advances · 2021Review
- Oxidative and Non-Oxidative Antimicrobial Activities of the Granzymes.Frontiers in immunology · 2021Review
- Cytotoxic Lymphocytes Target HIV-1 Gag Through Granzyme M-Mediated Cleavage.Frontiers in immunology · 2021Article
- New RNA Structural Elements Identified in the Coding Region of the Coxsackie B3 Virus Genome.Viruses · 2020Article
- Killer cell proteases can target viral immediate-early proteins to control human cytomegalovirus infection in a noncytotoxic manner.PLoS pathogens · 2020Article
- Interferon-Gamma Modulation of the Local T Cell Response to Alphavirus Encephalomyelitis.Viruses · 2020Article
- Review
- Cytomegalovirus-Infected Cells Resist T Cell Mediated Killing in an HLA-Recognition Independent Manner.Frontiers in microbiology · 2016Article
- Perforin and granzymes: function, dysfunction and human pathology.Nature reviews. Immunology · 2015Review
- Arginine methylation of hnRNPK negatively modulates apoptosis upon DNA damage through local regulation of phosphorylation.Nucleic acids research · 2014Article
- NK cell intrinsic regulation of MIP-1α by granzyme M.Cell death & disease · 2014Article
- Granzyme M: behind enemy lines.Cell death and differentiation · 2014Review
- A human proteome microarray identifies that the heterogeneous nuclear ribonucleoprotein K (hnRNP K) recognizes the 5' terminal sequence of the hepatitis C virus RNA.Molecular & cellular proteomics : MCP · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human cytomegalovirus (HCMV) is the most frequent viral cause of congenital defects and HCMV infection in immunocompromised patients may trigger devastating disease. Cytotoxic lymphocytes control HCMV by releasing granzymes towards virus-infected cells. In mice, granzyme M (GrM) has a physiological role in controlling murine CMV infection. However, the underlying mechanism remains poorly understood. In this study, we showed that human GrM was expressed by HCMV-specific CD8(+) T cells both in latently infected healthy individuals and in transplant patients during primary HCMV infection. We identified host cell heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a physiological GrM substrate. GrM most efficiently cleaved hnRNP K in the presence of RNA at multiple sites, thereby likely destroying hnRNP K function. Host cell hnRNP K was essential for HCMV replication not only by promoting viability of HCMV-infected cells but predominantly by regulating viral immediate-early 2 (IE2) protein levels. Furthermore, hnRNP K interacted with IE2 mRNA. Finally, GrM decreased IE2 protein expression in HCMV-infected cells. Our data suggest that targeting of hnRNP K by GrM contributes to the mechanism by which cytotoxic lymphocytes inhibit HCMV replication. This is the first evidence that cytotoxic lymphocytes target host cell proteins to control HCMV infections.
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