Human Cytomegalovirus Tegument Protein UL82 Inhibits STING-Mediated Signaling to Evade Antiviral Immunity

Cell Host and Microbe

Volumn 21, Issue 2, 2017, Pages 231-243

  Fu, Yu Zhi ^a   Su, Shan ^b   Gao, Yi Qun ^a   Wang, Pei Pei ^b   Huang, Zhe Fu ^c   Hu, Ming Ming ^b   Luo, Wei Wei ^b   Li, Shu ^a   Luo, Min Hua ^c   Wang, Yan Yi ^c   Shu, Hong Bing ^a,b  

^a WUHAN UNIVERSITY   (China)

^b WUHAN UNIVERSITY   (China)

^c WUHAN INSTITUTE OF VIROLOGY   (China)

Author keywords

cGAS; HCMV; immune evasion; innate immunity; iRhom2; MITA; STING; UL82; virus

Indexed keywords

HUMAN CYTOMEGALOVIRUS TEGUMENT PROTEIN UL82; INTERFERON REGULATORY FACTOR 3; PROTEIN; UNCLASSIFIED DRUG; CYTOMEGALOVIRUS PHOSPHOPROTEIN 71KDA; IRF3 PROTEIN, HUMAN; MEMBRANE PROTEIN; MPYS PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE; TBK1 PROTEIN, HUMAN; VIRAL PROTEIN;

ARTICLE; CELL MIGRATION; COMPLEX FORMATION; CONTROLLED STUDY; GENE TRANSLOCATION; HEK293 CELL LINE; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; IMMUNE EVASION; INNATE IMMUNITY; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; VIRUS IMMUNITY; VIRUS REPLICATION; CYTOMEGALOVIRUS; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PHYSIOLOGY; PROTEIN TRANSPORT;

CYTOMEGALOVIRUS; GENE EXPRESSION REGULATION, VIRAL; HUMANS; IMMUNE EVASION; IMMUNITY, INNATE; INTERFERON REGULATORY FACTOR-3; MEMBRANE PROTEINS; PROTEIN TRANSPORT; PROTEIN-SERINE-THREONINE KINASES; SIGNAL TRANSDUCTION; VIRAL PROTEINS; VIRUS REPLICATION;

EID: 85010877191     PISSN: 19313128     EISSN: 19346069     Source Type: Journal    
DOI: 10.1016/j.chom.2017.01.001     Document Type: Article

References (54)

1. Amsler, L., Verweij, M.C., DeFilippis, V.R., The tiers and dimensions of evasion of the type I interferon response by human cytomegalovirus. J. Mol. Biol. 425 (2013), 4857–4871.
2. An, T., Li, S., Pan, W., Tien, P., Zhong, B., Shu, H.B., Wu, S., DYRK2 Negatively Regulates Type I Interferon Induction by Promoting TBK1 Degradation via Ser527 Phosphorylation. PLoS Pathog., 11, 2015, e1005179.
3. Biron, K.K., Antiviral drugs for cytomegalovirus diseases. Antiviral Res. 71 (2006), 154–163.
4. Bresnahan, W.A., Shenk, T.E., UL82 virion protein activates expression of immediate early viral genes in human cytomegalovirus-infected cells. Proc. Natl. Acad. Sci. USA 97 (2000), 14506–14511.
5. Browne, E.P., Shenk, T., Human cytomegalovirus UL83-coded pp65 virion protein inhibits antiviral gene expression in infected cells. Proc. Natl. Acad. Sci. USA 100 (2003), 11439–11444.
6. Caffarelli, N., Fehr, A.R., Yu, D., Cyclin A degradation by primate cytomegalovirus protein pUL21a counters its innate restriction of virus replication. PLoS Pathog., 9, 2013, e1003825.
7. Cantrell, S.R., Bresnahan, W.A., Interaction between the human cytomegalovirus UL82 gene product (pp71) and hDaxx regulates immediate-early gene expression and viral replication. J. Virol. 79 (2005), 7792–7802.
8. Cheeran, M.C., Lokensgard, J.R., Schleiss, M.R., Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention. Clin. Microbiol. Rev. 22 (2009), 99–126.
9. Chen, L.T., Hu, M.M., Xu, Z.S., Liu, Y., Shu, H.B., MSX1 Modulates RLR-Mediated Innate Antiviral Signaling by Facilitating Assembly of TBK1-Associated Complexes. J. Immunol. 197 (2016), 199–207.
10. Christensen, M.H., Jensen, S.B., Miettinen, J.J., Luecke, S., Prabakaran, T., Reinert, L.S., Mettenleiter, T., Chen, Z.J., Knipe, D.M., Sandri-Goldin, R.M., et al. HSV-1 ICP27 targets the TBK1-activated STING signalsome to inhibit virus-induced type I IFN expression. EMBO J. 35 (2016), 1385–1399.
11. Cristea, I.M., Moorman, N.J., Terhune, S.S., Cuevas, C.D., O'Keefe, E.S., Rout, M.P., Chait, B.T., Shenk, T., Human cytomegalovirus pUL83 stimulates activity of the viral immediate-early promoter through its interaction with the cellular IFI16 protein. J. Virol. 84 (2010), 7803–7814.
12. Fu, Y.R., Liu, X.J., Li, X.J., Shen, Z.Z., Yang, B., Wu, C.C., Li, J.F., Miao, L.F., Ye, H.Q., Qiao, G.H., et al. MicroRNA miR-21 attenuates human cytomegalovirus replication in neural cells by targeting Cdc25a. J. Virol. 89 (2015), 1070–1082.
13. Hensel, G.M., Meyer, H.H., Buchmann, I., Pommerehne, D., Schmolke, S., Plachter, B., Radsak, K., Kern, H.F., Intracellular localization and expression of the human cytomegalovirus matrix phosphoprotein pp71 (ppUL82): evidence for its translocation into the nucleus. J. Gen. Virol. 77 (1996), 3087–3097.
14. Hu, M.M., Yang, Q., Zhang, J., Liu, S.M., Zhang, Y., Lin, H., Huang, Z.F., Wang, Y.Y., Zhang, X.D., Zhong, B., Shu, H.B., TRIM38 inhibits TNFα- and IL-1β-triggered NF-κB activation by mediating lysosome-dependent degradation of TAB2/3. Proc. Natl. Acad. Sci. USA 111 (2014), 1509–1514.
15. Hu, M.M., Xie, X.Q., Yang, Q., Liao, C.Y., Ye, W., Lin, H., Shu, H.B., TRIM38 Negatively Regulates TLR3/4-Mediated Innate Immune and Inflammatory Responses by Two Sequential and Distinct Mechanisms. J. Immunol. 195 (2015), 4415–4425.
16. Hu, M.M., Yang, Q., Xie, X.Q., Liao, C.Y., Lin, H., Liu, T.T., Yin, L., Shu, H.B., Sumoylation Promotes the Stability of the DNA Sensor cGAS and the Adaptor STING to Regulate the Kinetics of Response to DNA Virus. Immunity 45 (2016), 555–569.
17. Ishikawa, H., Barber, G.N., STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455 (2008), 674–678.
18. Ishikawa, H., Ma, Z., Barber, G.N., STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461 (2009), 788–792.
19. Kalejta, R.F., Shenk, T., Proteasome-dependent, ubiquitin-independent degradation of the Rb family of tumor suppressors by the human cytomegalovirus pp71 protein. Proc. Natl. Acad. Sci. USA 100 (2003), 3263–3268.
20. Kanda, T., Furuse, Y., Oshitani, H., Kiyono, T., Highly Efficient CRISPR/Cas9-Mediated Cloning and Functional Characterization of Gastric Cancer-Derived Epstein-Barr Virus Strains. J. Virol. 90 (2016), 4383–4393.
21. Konno, H., Konno, K., Barber, G.N., Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling. Cell 155 (2013), 688–698.
22. Lau, L., Gray, E.E., Brunette, R.L., Stetson, D.B., DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway. Science 350 (2015), 568–571.
23. Lei, C.Q., Zhong, B., Zhang, Y., Zhang, J., Wang, S., Shu, H.B., Glycogen synthase kinase 3β regulates IRF3 transcription factor-mediated antiviral response via activation of the kinase TBK1. Immunity 33 (2010), 878–889.
24. Li, Y., Chen, R., Zhou, Q., Xu, Z., Li, C., Wang, S., Mao, A., Zhang, X., He, W., Shu, H.B., LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection. Proc. Natl. Acad. Sci. USA 109 (2012), 11770–11775.
25. Li, T., Chen, J., Cristea, I.M., Human cytomegalovirus tegument protein pUL83 inhibits IFI16-mediated DNA sensing for immune evasion. Cell Host Microbe 14 (2013), 591–599.
26. Li, X.J., Liu, X.J., Yang, B., Fu, Y.R., Zhao, F., Shen, Z.Z., Miao, L.F., Rayner, S., Chavanas, S., Zhu, H., et al. Human Cytomegalovirus Infection Dysregulates the Localization and Stability of NICD1 and Jag1 in Neural Progenitor Cells. J. Virol. 89 (2015), 6792–6804.
27. Li, Z., Liu, G., Sun, L., Teng, Y., Guo, X., Jia, J., Sha, J., Yang, X., Chen, D., Sun, Q., PPM1A regulates antiviral signaling by antagonizing TBK1-mediated STING phosphorylation and aggregation. PLoS Pathog., 11, 2015, e1004783.
28. Liu, T.T., Yang, Q., Li, M., Zhong, B., Ran, Y., Liu, L.L., Yang, Y., Wang, Y.Y., Shu, H.B., LSm14A Plays a Critical Role in Antiviral Immune Responses by Regulating MITA Level in a Cell-Specific Manner. J. Immunol. 196 (2016), 5101–5111.
29. Luo, W.W., Li, S., Li, C., Lian, H., Yang, Q., Zhong, B., Shu, H.B., iRhom2 is essential for innate immunity to DNA viruses by mediating trafficking and stability of the adaptor STING. Nat. Immunol. 17 (2016), 1057–1066.
30. Ma, Z., Jacobs, S.R., West, J.A., Stopford, C., Zhang, Z., Davis, Z., Barber, G.N., Glaunsinger, B.A., Dittmer, D.P., Damania, B., Modulation of the cGAS-STING DNA sensing pathway by gammaherpesviruses. Proc. Natl. Acad. Sci. USA 112 (2015), E4306–E4315.
31. Mathers, C., Schafer, X., Martínez-Sobrido, L., Munger, J., The human cytomegalovirus UL26 protein antagonizes NF-κB activation. J. Virol. 88 (2014), 14289–14300.
32. Moorman, N.J., Cristea, I.M., Terhune, S.S., Rout, M.P., Chait, B.T., Shenk, T., Human cytomegalovirus protein UL38 inhibits host cell stress responses by antagonizing the tuberous sclerosis protein complex. Cell Host Microbe 3 (2008), 253–262.
33. Murphy, E., Rigoutsos, I., Shibuya, T., Shenk, T.E., Reevaluation of human cytomegalovirus coding potential. Proc. Natl. Acad. Sci. USA 100 (2003), 13585–13590.
34. Murphy, E., Yu, D., Grimwood, J., Schmutz, J., Dickson, M., Jarvis, M.A., Hahn, G., Nelson, J.A., Myers, R.M., Shenk, T.E., Coding potential of laboratory and clinical strains of human cytomegalovirus. Proc. Natl. Acad. Sci. USA 100 (2003), 14976–14981.
35. Paijo, J., Döring, M., Spanier, J., Grabski, E., Nooruzzaman, M., Schmidt, T., Witte, G., Messerle, M., Hornung, V., Kaever, V., Kalinke, U., cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells. PLoS Pathog., 12, 2016, e1005546.
36. Penkert, R.R., Kalejta, R.F., Nuclear localization of tegument-delivered pp71 in human cytomegalovirus-infected cells is facilitated by one or more factors present in terminally differentiated fibroblasts. J. Virol. 84 (2010), 9853–9863.
37. Ran, Y., Shu, H.B., Wang, Y.Y., MITA/STING: a central and multifaceted mediator in innate immune response. Cytokine Growth Factor Rev. 25 (2014), 631–639.
38. Saffert, R.T., Kalejta, R.F., Inactivating a cellular intrinsic immune defense mediated by Daxx is the mechanism through which the human cytomegalovirus pp71 protein stimulates viral immediate-early gene expression. J. Virol. 80 (2006), 3863–3871.
39. Saitoh, T., Fujita, N., Hayashi, T., Takahara, K., Satoh, T., Lee, H., Matsunaga, K., Kageyama, S., Omori, H., Noda, T., et al. Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc. Natl. Acad. Sci. USA 106 (2009), 20842–20846.
40. Shen, W., Westgard, E., Huang, L., Ward, M.D., Osborn, J.L., Chau, N.H., Collins, L., Marcum, B., Koach, M.A., Bibbs, J., et al. Nuclear trafficking of the human cytomegalovirus pp71 (ppUL82) tegument protein. Virology 376 (2008), 42–52.
41. Shu, H.B., Wang, Y.Y., Adding to the STING. Immunity 41 (2014), 871–873.
42. Söderberg-Nauclér, C., Does cytomegalovirus play a causative role in the development of various inflammatory diseases and cancer?. J. Intern. Med. 259 (2006), 219–246.
43. Sun, W., Li, Y., Chen, L., Chen, H., You, F., Zhou, X., Zhou, Y., Zhai, Z., Chen, D., Jiang, Z., ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization. Proc. Natl. Acad. Sci. USA 106 (2009), 8653–8658.
44. Sun, L., Wu, J., Du, F., Chen, X., Chen, Z.J., Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339 (2013), 786–791.
45. Tanaka, Y., Chen, Z.J., STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Sci. Signal., 5, 2012, ra20.
46. Taylor, R.T., Bresnahan, W.A., Human cytomegalovirus immediate-early 2 gene expression blocks virus-induced beta interferon production. J. Virol. 79 (2005), 3873–3877.
47. van Diemen, F.R., Kruse, E.M., Hooykaas, M.J., Bruggeling, C.E., Schürch, A.C., van Ham, P.M., Imhof, S.M., Nijhuis, M., Wiertz, E.J., Lebbink, R.J., CRISPR/Cas9-Mediated Genome Editing of Herpesviruses Limits Productive and Latent Infections. PLoS Pathog., 12, 2016, e1005701.
48. Wu, J.J., Li, W., Shao, Y., Avey, D., Fu, B., Gillen, J., Hand, T., Ma, S., Liu, X., Miley, W., et al. Inhibition of cGAS DNA Sensing by a Herpesvirus Virion Protein. Cell Host Microbe 18 (2015), 333–344.
49. Xu, L.G., Wang, Y.Y., Han, K.J., Li, L.Y., Zhai, Z., Shu, H.B., VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol. Cell 19 (2005), 727–740.
50. Zhang, G., Chan, B., Samarina, N., Abere, B., Weidner-Glunde, M., Buch, A., Pich, A., Brinkmann, M.M., Schulz, T.F., Cytoplasmic isoforms of Kaposi sarcoma herpesvirus LANA recruit and antagonize the innate immune DNA sensor cGAS. Proc. Natl. Acad. Sci. USA 113 (2016), E1034–E1043.
51. Zhong, B., Yang, Y., Li, S., Wang, Y.Y., Li, Y., Diao, F., Lei, C., He, X., Zhang, L., Tien, P., Shu, H.B., The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 29 (2008), 538–550.
52. Zhong, B., Zhang, L., Lei, C., Li, Y., Mao, A.P., Yang, Y., Wang, Y.Y., Zhang, X.L., Shu, H.B., The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA. Immunity 30 (2009), 397–407.
53. Zhou, Q., Lin, H., Wang, S., Wang, S., Ran, Y., Liu, Y., Ye, W., Xiong, X., Zhong, B., Shu, H.B., Wang, Y.Y., The ER-associated protein ZDHHC1 is a positive regulator of DNA virus-triggered, MITA/STING-dependent innate immune signaling. Cell Host Microbe 16 (2014), 450–461.
54. Ziehr, B., Vincent, H.A., Moorman, N.J., Human Cytomegalovirus pTRS1 and pIRS1 Antagonize Protein Kinase R To Facilitate Virus Replication. J. Virol. 90 (2016), 3839–3848.