The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Human Cytomegalovirus Tegument Protein pUL83 Inhibits IFI16-Mediated DNA Sensing for Immune Evasion
Open accessAbstract
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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In the citing paper
“and of the pUL83-dependent inhibition of this sensing function (73)”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [73]
In the citing paper
“Recently, we identified eight phosphosites within immunoaffinity-isolated pUL83 and established that one phosphorylation, under the control of host kinases, functions to block pUL83-dependent dispersal of cellular innate immunity effectors (73).”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [73]
In the citing paper
“Recently, we identified eight phosphosites within immunoaffinity-isolated pUL83 and established that one phosphorylation, under the control of host kinases, functions to block pUL83-dependent dispersal of cellular innate immunity effectors (73).”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [73]
In the citing paper
“For instance, the DNA sensor IFI16 is an effector of innate immune responses during viral infection, detecting viral DNA in both the nucleus and the cytoplasm (71–73, 136, 137).”
From The Impact of Mass Spectrometry–Based Proteomics on Fundamental Discoveries in Virology (2014) · cites this paper as [73]
In the citing paper
“the major viral tegument protein during HCMV infection was shown to bind to IFI16 in the nucleus, thereby blocking its ability to oligomerize and initiate antiviral cytokine response.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [49]
In the citing paper
“For example, crosslinking was used to show that a host defense protein oligomerizes in response to viral infection [49].”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [49]
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Metadata
- Authors
- Li, T., Chen, J., & Cristea, I. M.
- Affiliations
- Princeton University (US)
- Corresponding author
- 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)
- 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
- 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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