Human cytomegalovirus protein UL42 antagonizes cGAS/MITA-mediated innate antiviral response.

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  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, c2005-
    • Subject Terms:
    • Abstract:
      Cyclic GMP-AMP synthase (cGAS) senses viral DNA in the cytosol and then catalyzes synthesis of the second messenger cGAMP, which activates the ER-localized adaptor protein Mediator of IRF3 Activator (MITA) to initiate innate antiviral response. Human cytomegalovirus (HCMV) proteins can antagonize host immune responses to promote latent infection. Here, we identified HCMV UL42 as a negative regulator of cGAS/MITA-dependent antiviral response. UL42-deficiency enhances HCMV-induced production of type I interferons (IFNs) and downstream antiviral genes. Consistently, wild-type HCMV replicates more efficiently than UL42-deficient HCMV. UL42 interacts with both cGAS and MITA. UL42 inhibits DNA binding, oligomerization and enzymatic activity of cGAS. UL42 also impairs translocation of MITA from the ER to perinuclear punctate structures, which is required for MITA activation, by facilitating p62/LC3B-mediated degradation of translocon-associated protein β (TRAPβ). These results suggest that UL42 can antagonize innate immune response to HCMV by targeting the core components of viral DNA-triggered signaling pathways.
      Competing Interests: The authors have declared that no competing interests exist.
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    • Accession Number:
      0 (Antiviral Agents)
      0 (DNA, Viral)
      0 (Membrane Proteins)
      0 (STING1 protein, human)
      0 (Viral Proteins)
      EC 2.7.7.- (Nucleotidyltransferases)
      EC 2.7.7.- (cGAS protein, human)
    • Publication Date:
      Date Created: 20190521 Date Completed: 20191107 Latest Revision: 20210226
    • Publication Date:
      20240104
    • Accession Number:
      PMC6527189
    • Accession Number:
      10.1371/journal.ppat.1007691
    • Accession Number:
      31107917