ArticlePLoS pathogens2020
Murine cytomegaloviruses m139 targets DDX3 to curtail interferon production and promote viral replication.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Breaking barriers: how cytomegaloviruses manipulate myeloid cells to invade tissues.EMBO reports · 2026Review
- At the crossroads of immunity and hijacking: dual roles of DDX proteins during host-virus interactions.Frontiers in cellular and infection microbiology · 2026Review
- Unconventional CD8Science advances · 2025Article
- RNA helicase DDX3X promotes NK cell survival by supporting MCL1 expression.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- DDX3X and virus interactions: functional diversity and antiviral strategies.Frontiers in microbiology · 2025Review
- Salivary gland macrophages in health and disease: heterogeneity, niche crosstalk, and therapeutic avenues.Frontiers in immunology · 2025Review
- DDX3X Promotes Rotavirus Infection and Serves as an Antiviral Target.Transboundary and emerging diseases · 2025Article
- E2F3-dependent activation of FAM111B restricts mouse cytomegalovirus replication in primate cells.Journal of virology · 2024Article
- Virological, innate, and adaptive immune profiles shaped by variation in route and age of host in murine cytomegalovirus infection.Journal of virology · 2024Article
- A cytomegalovirus inflammasome inhibitor reduces proinflammatory cytokine release and pyroptosis.Nature communications · 2024Article
- Analysis of the serum proteome profile of wild stump-tailed macaques (Frontiers in veterinary science · 2024Article
- Characterization of M116.1p, a Murine Cytomegalovirus Protein Required for Efficient Infection of Mononuclear Phagocytes.Journal of virology · 2022Article
- Mechanisms of Antiviral Cytotoxic CD4 T Cell Differentiation.Journal of virology · 2021Article
- RNA Helicase DDX3: A Double-Edged Sword for Viral Replication and Immune Signaling.Microorganisms · 2021Review
- Viral mediated tethering to SEL1L facilitates ER-associated degradation of IRE1.Journal of virology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytomegaloviruses (CMV) infect many different cell types and tissues in their respective hosts. Monocytes and macrophages play an important role in CMV dissemination from the site of infection to target organs. Moreover, macrophages are specialized in pathogen sensing and respond to infection by secreting cytokines and interferons. In murine cytomegalovirus (MCMV), a model for human cytomegalovirus, several genes required for efficient replication in macrophages have been identified, but their specific functions remain poorly understood. Here we show that MCMV m139, a gene of the conserved US22 gene family, encodes a protein that interacts with the DEAD box helicase DDX3, a protein involved in pathogen sensing and interferon (IFN) induction, and the E3 ubiquitin ligase UBR5. DDX3 and UBR5 also participate in the transcription, processing, and translation of a subset of cellular mRNAs. We show that m139 inhibits DDX3-mediated IFN-α and IFN-β induction and is necessary for efficient viral replication in bone-marrow derived macrophages. In vivo, m139 is crucial for viral dissemination to local lymph nodes and to the salivary glands. An m139-deficient MCMV also replicated to lower titers in SVEC4-10 endothelial cells. This replication defect was not accompanied by increased IFN-β transcription, but was rescued by knockout of either DDX3 or UBR5. Moreover, m139 co-localized with DDX3 and UBR5 in viral replication compartments in the cell nucleus. These results suggest that m139 inhibits DDX3-mediated IFN production in macrophages and antagonizes DDX3 and UBR5-dependent functions related to RNA metabolism in endothelial cells.
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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.