ArticleJournal of virology2008
Dominant-negative FADD rescues the in vivo fitness of a cytomegalovirus lacking an antiapoptotic viral gene.
Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 60 citations in OpenAlex.
- Mechanisms, regulation and clinical relevance of necroptosis.Nature reviews. Molecular cell biology · 2026Review
- Z-Nucleic Acid-Binding Protein (ZBP)1 (DAI/DLM1) Regulation in Antiviral Cell Death Pathways.Pathogens (Basel, Switzerland) · 2026Review
- The Interplay Between Viral Infection and Cell Death: A Ping-Pong Effect.Advances in virology · 2025Review
- No Time to Die: How Cytomegaloviruses Suppress Apoptosis, Necroptosis, and Pyroptosis.Viruses · 2024Review
- Cytomegalovirus inhibitors of programmed cell death restrict antigen cross-presentation in the priming of antiviral CD8 T cells.PLoS pathogens · 2024Article
- Human cytomegalovirus UL36 inhibits IRF3-dependent immune signaling to counterbalance its immunoenhancement as apoptotic inhibitor.Science advances · 2023Article
- Programmed Necrosis in Host Defense.Current topics in microbiology and immunology · 2023Article
- Retinal and Choroidal Pathologies in Aged BALB/c Mice Following Systemic Neonatal Murine Cytomegalovirus Infection.The American journal of pathology · 2021Article
- Article
- 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
- Caspase-8-dependent control of NK- and T cell responses during cytomegalovirus infection.Medical microbiology and immunology · 2019Review
- Remarkably Robust Antiviral Immune Response despite Combined Deficiency in Caspase-8 and RIPK3.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Human Cytomegalovirus Protein pUL38 Prevents Premature Cell Death by Binding to Ubiquitin-Specific Protease 24 and Regulating Iron Metabolism.Journal of virology · 2018Article
- Review
- RIPK3-driven cell death during virus infections.Immunological reviews · 2017Review
- Mouse cytomegalovirus M36 and M45 death suppressors cooperate to prevent inflammation resulting from antiviral programmed cell death pathways.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- UL36 Rescues Apoptosis Inhibition andFrontiers in cellular and infection microbiology · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genes that inhibit apoptosis have been described for many DNA viruses. Herpesviruses often contain even more than one gene to control cell death. Apoptosis inhibition by viral genes is postulated to contribute to viral fitness, although a formal proof is pending. To address this question, we studied the mouse cytomegalovirus (MCMV) protein M36, which binds to caspase-8 and blocks death receptor-induced apoptosis. The growth of MCMV recombinants lacking M36 (DeltaM36) was attenuated in vitro and in vivo. In vitro, caspase inhibition by zVAD-fmk blocked apoptosis in DeltaM36-infected macrophages and rescued the growth of the mutant. In vivo, DeltaM36 infection foci in liver tissue contained significantly more apoptotic hepatocytes and Kupffer cells than did revertant virus foci, and apoptosis occurred during the early phase of virus replication prior to virion assembly. To further delineate the mode of M36 function, we replaced the M36 gene with a dominant-negative FADD (FADD(DN)) in an MCMV recombinant. FADD(DN) was expressed in cells infected with the recombinant and blocked the death-receptor pathway, replacing the antiapoptotic function of M36. Most importantly, FADD(DN) rescued DeltaM36 virus replication, both in vitro and in vivo. These findings have identified the biological role of M36 and define apoptosis inhibition as a key determinant of viral fitness.
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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.