ArticlePLoS pathogens2012
Block of death-receptor apoptosis protects mouse cytomegalovirus from macrophages and is a determinant of virulence in immunodeficient hosts.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 41 citations in OpenAlex.
- Z-Nucleic Acid-Binding Protein (ZBP)1 (DAI/DLM1) Regulation in Antiviral Cell Death Pathways.Pathogens (Basel, Switzerland) · 2026Review
- Uterine natural killer cell-mediated immune imbalance impairs uterine vascular remodeling and contributes to adverse pregnancy outcomes in dengue virus-infected mice.Microbiology spectrum · 2026Article
- Breaking barriers: how cytomegaloviruses manipulate myeloid cells to invade tissues.EMBO reports · 2026Review
- The Immunoregulatory Mechanisms of Human Cytomegalovirus from Primary Infection to Reactivation.Pathogens (Basel, Switzerland) · 2025Review
- Programmed cell death: molecular mechanisms, biological functions, diseases, and therapeutic targets.MedComm · 2024Review
- The battle between host antiviral innate immunity and immune evasion by cytomegalovirus.Cellular and molecular life sciences : CMLS · 2024Review
- No Time to Die: How Cytomegaloviruses Suppress Apoptosis, Necroptosis, and Pyroptosis.Viruses · 2024Review
- Mouse cytomegalovirus lacking sgg1 shows reduced import into the salivary glands.The Journal of general virology · 2024Article
- Cytomegalovirus inhibitors of programmed cell death restrict antigen cross-presentation in the priming of antiviral CD8 T cells.PLoS pathogens · 2024Article
- Pseudorabies virus gM and its homologous proteins in herpesviruses induce mitochondria-related apoptosis involved in viral pathogenicity.PLoS pathogens · 2024Article
- Caspase cleavage of RIPK3 after AspCell death and differentiation · 2024Article
- Human cytomegalovirus UL36 inhibits IRF3-dependent immune signaling to counterbalance its immunoenhancement as apoptotic inhibitor.Science advances · 2023Article
- Characterization of M116.1p, a Murine Cytomegalovirus Protein Required for Efficient Infection of Mononuclear Phagocytes.Journal of virology · 2022Article
- Article
- Cell death signalling in virus infection.Cellular signalling · 2020Review
- TNF Signaling Dictates Myeloid and Non-Myeloid Cell Crosstalk to Execute MCMV-Induced Extrinsic Apoptosis.Viruses · 2020Article
- Murine cytomegaloviruses m139 targets DDX3 to curtail interferon production and promote viral replication.PLoS pathogens · 2020Article
- Cytomegalovirus inhibition of extrinsic apoptosis determines fitness and resistance to cytotoxic CD8 T cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Cytomegaloviruses and Macrophages-Friends and Foes From Early on?Frontiers in immunology · 2020Review
- The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis.International review of cell and molecular biology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inhibition of death-receptor apoptosis is a conserved viral function. The murine cytomegalovirus (MCMV) gene M36 is a sequence and functional homologue of the human cytomegalovirus gene UL36, and it encodes an inhibitor of apoptosis that binds to caspase-8, blocks downstream signaling and thus contributes to viral fitness in macrophages and in vivo. Here we show a direct link between the inability of mutants lacking the M36 gene (ΔM36) to inhibit apoptosis, poor viral growth in macrophage cell cultures and viral in vivo fitness and virulence. ΔM36 grew poorly in RAG1 knockout mice and in RAG/IL-2-receptor common gamma chain double knockout mice (RAGγC(-/-)), but the depletion of macrophages in either mouse strain rescued the growth of ΔM36 to almost wild-type levels. This was consistent with the observation that activated macrophages were sufficient to impair ΔM36 growth in vitro. Namely, spiking fibroblast cell cultures with activated macrophages had a suppressive effect on ΔM36 growth, which could be reverted by z-VAD-fmk, a chemical apoptosis inhibitor. TNFα from activated macrophages synergized with IFNγ in target cells to inhibit ΔM36 growth. Hence, our data show that poor ΔM36 growth in macrophages does not reflect a defect in tropism, but rather a defect in the suppression of antiviral mediators secreted by macrophages. To the best of our knowledge, this shows for the first time an immune evasion mechanism that protects MCMV selectively from the antiviral activity of macrophages, and thus critically contributes to viral pathogenicity in the immunocompromised host devoid of the adaptive immune system.
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