Cited by 226interferon and immune responsesCytomegalovirus and herpesvirus researchImmune Response and Inflammation

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Human Cytomegalovirus Tegument Protein pUL83 Inhibits IFI16-Mediated DNA Sensing for Immune Evasion

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Li, Tuo, Chen, Jin, Cristea, Ileana M.·2013·Cell Host & Microbe

DOI 10.1016/j.chom.2013.10.007PMC PMC3876934

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Abstract

Nuclear sensing of viral DNA has emerged as an essential step in innate immune responses against herpesviruses. Here, we provide mechanistic insight into host recognition of human cytomegalovirus (HCMV) and subsequent immune evasion by this prominent DNA virus. We establish that the interferon-inducible protein IFI16 acts as a nuclear DNA sensor following HCMV infection, binding viral DNA and triggering expression of antiviral cytokines via the STING-TBK1-IRF3 signaling pathway. The HCMV tegument protein pUL83 inhibits this response by interacting with the IFI16 pyrin domain, blocking its oligomerization upon DNA sensing and subsequent immune signals. pUL83 disrupts IFI16 by concerted action of its N- and C-terminal domains, in which an evolutionarily conserved N-terminal pyrin association domain (PAD) binds IFI16. Additionally, phosphorylation of the N-terminal domain modulates pUL83-mediated inhibition of pyrin aggregation. Collectively, our data elucidate the interplay between host DNA sensing and HCMV immune evasion, providing targets for restoring antiviral immunity.

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Authors: Li, T., Chen, J., & Cristea, I. M.
Affiliations: Princeton University (US)
Corresponding author: Cristea, Ileana M.
ORCID: Li, Tuo
Chen, Jin
Cristea, Ileana M.
Venue: Cell Host & Microbe
Publisher: Elsevier BV
Published: 2013-11
Volume: 14
Issue: 5
Pages: 591-599
ISSN: 1931-3128 (ISSN-L)
DOI: 10.1016/j.chom.2013.10.007
PMC: PMC3876934
OpenAlex: W2033448230
Cited by: 226
References: 30
Citations by year: 2026: 3 · 2025: 10 · 2024: 11 · 2023: 11 · 2022: 13 · 2021: 23 · 2020: 21 · 2019: 21 · 2018: 21 · 2017: 19 · 2016: 29 · 2015: 25 · 2014: 18 · 2013: 1
FWCI: 13.47
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 377 d)
Locations: Cell Host & Microbe (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Drug Abuse (DP1DA026192)
National Institute of Allergy and Infectious Diseases (R21AI102187)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD073044)
Topics: Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: human cytomegalovirus, tegument proteins, IFI16, pyrin domain, immune evasion, herpesvirus, protein phosphorylation, antiviral cytokines, innate immunity
MeSH terms: Cell Line, Cytomegalovirus, DNA, Viral, Humans, Nuclear Proteins, Phosphoproteins, Protein Binding, Viral Matrix Proteins, Signal Transduction, Protein Interaction Domains and Motifs, Host-Pathogen Interactions, Immune Evasion

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Human Cytomegalovirus Tegument Protein pUL83 Inhibits IFI16-Mediated DNA Sensing for Immune Evasion

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