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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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“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
“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
“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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Cites
Seth, R. B., Sun, L., Ea, C.-K., & Chen, Z. J. (2005) · Cell · doi:10.1016/j.cell.2005.08.012 · Cited by 3,329
AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC
Hornung, V., Ablasser, A., Charrel-Dennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E., & Fitzgerald, K. A. (2009) · Nature · doi:10.1038/nature07725 · Cited by 2,627
AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA
Fernandes-Alnemri, T., Yu, J.-W., Datta, P., Wu, J., & Alnemri, E. S. (2009) · Nature · doi:10.1038/nature07710 · Cited by 1,831
IFI16 is an innate immune sensor for intracellular DNA
Unterholzner, L., Keating, S. E., Baran, M., Horan, K. A., Jensen, S. B., Sharma, S., Sirois, C. M., Jin, T., Latz, E., Xiao, T. S., et al. (2010) · Nature Immunology · doi:10.1038/ni.1932 · Cited by 1,643
Kerur, N., Veettil, M. V., Sharma-Walia, N., Bottero, V., Sadagopan, S., Otageri, P., & Chandran, B. (2011) · Cell Host & Microbe · doi:10.1016/j.chom.2011.04.008 · Cited by 702
Jin, T., Perry, A., Jiang, J., Smith, P. T., Curry, J. A., Unterholzner, L., Jiang, Z., Horvath, G. L., Rathinam, V. A. K., Johnstone, R. W., et al. (2012) · Immunity · doi:10.1016/j.immuni.2012.02.014 · Cited by 610
Identification of Proteins in Human Cytomegalovirus (HCMV) Particles: the HCMV Proteome
Varnum, S. M., Streblow, D. N., Monroe, M. E., Smith, P., Auberry, K. J., Paša-Tolić, L., Wang, D., Camp, D. G., Rodland, K., Wiley, S., et al. (2004) · Journal of Virology · doi:10.1128/jvi.78.20.10960-10966.2004 · Cited by 598
Cheeran, M. C. ‐., Lokensgard, J. R., & Schleiss, M. R. (2009) · Clinical Microbiology Reviews · doi:10.1128/cmr.00023-08 · Cited by 517
Orzalli, M. H., DeLuca, N. A., & Knipe, D. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211302109 · Cited by 422
Jiang, X., Kinch, L. N., Brautigam, C. A., Chen, X., Du, F., Grishin, N. V., & Chen, Z. J. (2012) · Immunity · doi:10.1016/j.immuni.2012.03.022 · Cited by 407
Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus
Arnon, T. I., Achdout, H., Levi, O., Markel, G., Saleh, N., Katz, G., Gazit, R., Gonen‐Gross, T., Hanna, J. H., Nahari, E., et al. (2005) · Nature Immunology · doi:10.1038/ni1190 · Cited by 396
Li, T., Diner, B. A., Chen, J., & Cristea, I. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1203447109 · Cited by 297
Self-citationGilbert, M. J., Riddell, S. R., Plachter, B., & Greenberg, P. D. (1996) · Nature · doi:10.1038/383720a0 · Cited by 279
Johnson, K. E., Chikoti, L., & Chandran, B. (2013) · Journal of Virology · doi:10.1128/jvi.00082-13 · Cited by 271
Fluorescent Proteins as Proteomic Probes
Cristea, I. M., Williams, R., Chait, B. T., & Rout, M. P. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500227-mcp200 · Cited by 251
Self-citationGariano, G. R., Dell'Oste, V., Bronzini, M., Gatti, D., Luganini, A., De Andrea, M., Gribaudo, G., Gariglio, M., & Landolfo, S. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002498 · Cited by 227
Ansari, M. A., Singh, V. V., Dutta, S., Veettil, M. V., Dutta, D., Leela, C., Lu, J. L., Everly, D. N., & Chandran, B. (2013) · Journal of Virology · doi:10.1128/jvi.00805-13 · Cited by 213
Horan, K., Hansen, K., Jakobsen, M. R., Holm, C. K., Søby, S., Unterholzner, L., Thompson, M., West, J. A., Iversen, M. B., Rasmussen, S. B., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202749 · Cited by 212
Browne, E. P., & Shenk, T. E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1534570100 · Cited by 201
Abate, D. A., Watanabe, S., & Mocarski, E. S. (2004) · Journal of Virology · doi:10.1128/jvi.78.20.10995-11006.2004 · Cited by 197
Paulus, C., Krauss, S., & Nevels, M. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600007103 · Cited by 178
Singh, V. V., Kerur, N., Bottero, V., Dutta, S., Chakraborty, S., Ansari, M. A., Paudel, N., Leela, C., & Chandran, B. (2013) · Journal of Virology · doi:10.1128/jvi.03282-12 · Cited by 160
Cristea, I. M., Moorman, N. J., Terhune, S. S., Cuevas, C. D., O'Keefe, E. S., Rout, M. P., Chait, B. T., & Shenk, T. (2010) · Journal of Virology · doi:10.1128/jvi.00139-10 · Cited by 155
Self-citationParamyxovirus V Proteins Disrupt the Fold of the RNA Sensor MDA5 to Inhibit Antiviral Signaling
Motz, C., Schuhmann, K. M., Kirchhofer, A., Moldt, M., Witte, G., Conzelmann, K., & Hopfner, K. (2013) · Science · doi:10.1126/science.1230949 · Cited by 125
Jabs, D. A., Enger, C. L., Forman, M., Dunn, J. P., Retinitis, F. T. C., & Viral Resistance Study Group (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.9.2240 · Cited by 124
Roby, C., & Gibson, W. (1986) · Journal of Virology · doi:10.1128/jvi.59.3.714-727.1986 · Cited by 119
Taylor, R. T., & Bresnahan, W. A. (2005) · Journal of Virology · doi:10.1128/jvi.79.6.3873-3877.2005 · Cited by 119
Human Cytomegalovirus Immediate-Early 2 Protein IE86 Blocks Virus-Induced Chemokine Expression
Taylor, R. T., & Bresnahan, W. A. (2005) · Journal of Virology · doi:10.1128/jvi.80.2.920-928.2006 · Cited by 95
Innate Immune Messenger 2-5A Tethers Human RNase L into Active High-Order Complexes
Han, Y., Whitney, G., Donovan, J., & Korennykh, A. V. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.09.004 · Cited by 55
McGregor, A., Liu, F., & Schleiss, M. R. (2004) · Journal of Virology · doi:10.1128/jvi.78.18.9872-9889.2004 · Cited by 38
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Ma, Z., & Damania, B. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.01.010 · Cited by 450
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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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