ArticleProceedings of the National Academy of Sciences of the United States of America2017
Mouse cytomegalovirus M36 and M45 death suppressors cooperate to prevent inflammation resulting from antiviral programmed cell death pathways.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 64 citations in OpenAlex.
- Biological consequences of Z-nucleic acid sensing by ZBP1 and ADAR1.RNA biology · 2026Review
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- UL45 of Human Cytomegalovirus Promotes Macrophage Survival and Modulates RIPK3-Associated Cell Death.Viruses · 2026Article
- Z-Nucleic Acid-Binding Protein (ZBP)1 (DAI/DLM1) Regulation in Antiviral Cell Death Pathways.Pathogens (Basel, Switzerland) · 2026Review
- Breaking barriers: how cytomegaloviruses manipulate myeloid cells to invade tissues.EMBO reports · 2026Review
- Human cytomegalovirus-triggered necroptosis is suppressed by sequestration of MLKL in the nucleus of infected monocytes.Journal of virology · 2025Article
- Molecular features of congenital cytomegalovirus infection in neonatal mouse brain at single-cell resolution.Acta neuropathologica communications · 2025Article
- Review
- Cytomegalovirus inhibitors of programmed cell death restrict antigen cross-presentation in the priming of antiviral CD8 T cells.PLoS pathogens · 2024Article
- Caspase cleavage of RIPK3 after AspCell death and differentiation · 2024Article
- CSFV restricts necroptosis to sustain infection by inducing autophagy/mitophagy-targeted degradation of RIPK3.Microbiology spectrum · 2024Article
- Role of Necroptosis in Intervertebral Disc Degeneration.International journal of molecular sciences · 2023Review
- Differential effects of CMV infection on the viability of cardiac cells.Cell death discovery · 2023Article
- Resistance To Poxvirus Lethality Does Not Require the Necroptosis Proteins RIPK3 or MLKL.Journal of virology · 2023Article
- The double-edged functions of necroptosis.Cell death & disease · 2023Review
- Approaches to Evaluating Necroptosis in Virus-Infected Cells.Sub-cellular biochemistry · 2023Article
- Programmed Necrosis in Host Defense.Current topics in microbiology and immunology · 2023Article
- Cell death proteins in sepsis: key players and modern therapeutic approaches.Frontiers in immunology · 2023Review
- Non-Apoptotic Programmed Cell Death in Thyroid Diseases.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Viral-mediated activation and inhibition of programmed cell death.PLoS pathogens · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The complex interplay between caspase-8 and receptor-interacting protein (RIP) kinase RIP 3 (RIPK3) driving extrinsic apoptosis and necroptosis is not fully understood. Murine cytomegalovirus triggers both apoptosis and necroptosis in infected cells; however, encoded inhibitors of caspase-8 activity (M36) and RIP3 signaling (M45) suppress these antiviral responses. Here, we report that this virus activates caspase-8 in macrophages to trigger apoptosis that gives rise to secondary necroptosis. Infection with double-mutant ΔM36/M45mutRHIM virus reveals a signaling pattern in which caspase-8 activates caspase-3 to drive apoptosis with subsequent RIP3-dependent activation of mixed lineage kinase domain-like (MLKL) leading to necroptosis. This combined cell death signaling is highly inflammatory, greater than either apoptosis induced by ΔM36 or necroptosis induced by M45mutRHIM virus. IL-6 production by macrophages is dramatically increased during double-mutant virus infection and correlates with faster antiviral responses in the host. Collaboratively, M36 and M45 target caspase-8 and RIP3 pathways together to suppress this proinflammatory cell death. This study reveals the effect of antiviral programmed cell death pathways on inflammation, shows that caspase-8 activation may go hand-in-hand with necroptosis in macrophages, and revises current understanding of independent and collaborative functions of M36 and M45 in blocking apoptotic and necroptotic cell death responses.
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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.