Human cytomegalovirus tegument protein pp65 (pUL83) dampens type I interferon production by inactivating the DNA sensor cGAS without affecting STING

Journal of Virology

Volumn 92, Issue 6, 2018, Pages

  Biolatti, Matteo ^a   Dell'Oste, Valentina ^a   Pautasso, Sara ^a   Gugliesi, Francesca ^a   von Einem, Jens ^b   Krapp, Christian ^c   Jakobsen, Martin Roelsgaard ^c   Borgogna, Cinzia ^d   Gariglio, Marisa ^d   De Andrea, Marco ^a,d   Landolfo, Santo ^a  

^a UNIVERSITY OF TURIN   (Italy)

^b UNIVERSITY HOSPITAL ULM   (Germany)

^c AARHUS UNIVERSITY   (Denmark)

^d Azienda Ospedaliero Universitaria Maggiore della Carità   (Italy)

Author keywords

CGAS; Human cytomegalovirus; IFI16; Innate immunity; Interactome; Interferons; pp65; STING

Indexed keywords

BETA INTERFERON; CYCLIC GMP AMP SYNTHASE; CYTOMEGALOVIRUS ANTIGEN PP65; INTERFERON; INTERFERON REGULATORY FACTOR 3; MESSENGER RNA; PROTEASOME; PROTEIN STING; UNCLASSIFIED DRUG; VIRAL PROTEIN; CYTOMEGALOVIRUS MATRIX PROTEIN 65KDA; MATRIX PROTEIN; MB21D1 PROTEIN, HUMAN; MEMBRANE PROTEIN; MPYS PROTEIN, HUMAN; NUCLEOTIDYLTRANSFERASE; PHOSPHOPROTEIN; PROTEIN BINDING;

ARTICLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOMEGALOVIRUS INFECTION; ENZYME ACTIVITY; GENE EXPRESSION LEVEL; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; IFN BETA GENE; IMMUNE EVASION; IMMUNOPRECIPITATION; INNATE IMMUNITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN PROTEIN INTERACTION; RESIDUE ANALYSIS; SKIN FIBROBLAST; UBIQUITINATION; VIRUS STRAIN; CYTOMEGALOVIRUS; GENETICS; HEK293 CELL LINE; IMMUNOLOGY; PATHOLOGY; SIGNAL TRANSDUCTION;

CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; HEK293 CELLS; HUMANS; IMMUNE EVASION; IMMUNITY, INNATE; INTERFERON TYPE I; MEMBRANE PROTEINS; NUCLEOTIDYLTRANSFERASES; PHOSPHOPROTEINS; PROTEIN BINDING; SIGNAL TRANSDUCTION; VIRAL MATRIX PROTEINS;

EID: 85042471176     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01774-17     Document Type: Article

References (70)

1. Britt WJ. 2017. Congenital human cytomegalovirus infection and the enigma of maternal immunity. J Virol 91:e02392-16. https://doi.org/10.1128/ JVI.02392-16
2. Griffiths P, Baraniak I, Reeves M. 2015. The pathogenesis of human cytomegalovirus. J Pathol 235:288-297. https://doi.org/10.1002/path.4437
3. McNab F, Mayer-Barber K, Sher A, Wack A, O'Garra A. 2015. Type I interferons in infectious disease. Nat Rev Immunol 15:87-103. https:// doi.org/10.1038/nri3787
4. Luecke S, Paludan SR. 2017. Molecular requirements for sensing of intracellular microbial nucleic acids by the innate immune system. Cytokine 98:4-14. https://doi.org/10.1016/j.cyto.2016.10.003
5. Dempsey A, Bowie AG. 2015. Innate immune recognition of DNA: a recent history. Virology 479-480:146-152. https://doi.org/10.1016/j.virol .2015.03.013
6. Komatsu T, Nagata K, Wodrich H. 2016. The role of nuclear antiviral factors against invading DNA viruses: the immediate fate of incoming viral genomes. Viruses 8:E290. https://doi.org/10.3390/v8100290
7. Zevini A, Olagnier D, Hiscott J. 2017. Crosstalk between cytoplasmic RIG-I and STING sensing pathways. Trends Immunol 38:194-205. https://doi .org/10.1016/j.it.2016.12.004
8. Takaoka A, Wang Z, Choi MK, Yanai H, Negishi H, Ban T, Lu Y, Miyagishi M, Kodama T, Honda K, Ohba Y, Taniguchi T. 2007. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 448:501-505. https://doi.org/10.1038/nature06013
9. Upton JW, Kaiser WJ, Mocarski ES. 2012. DAI/ZBP1/DLM-1 complexes with RIP3 to mediate virus-induced programmed necrosis that is targeted by murine cytomegalovirus vIRA. Cell Host Microbe 11:290-297. https://doi.org/10.1016/j.chom.2012.01.016
10. Li T, Diner BA, Chen J, Cristea IM. 2012. Acetylation modulates cellular distribution and DNA sensing ability of interferon-inducible protein IFI16. Proc Natl Acad Sci U S A 109:10558-10563. https://doi.org/10 .1073/pnas.1203447109
11. Horan KA, Hansen K, Jakobsen MR, Holm CK, Søby S, Unterholzner L, Thompson M, West JA, Iversen MB, Rasmussen SB, Ellermann-Eriksen S, Kurt-Jones E, Landolfo S, Damania B, Melchjorsen J, Bowie AG, Fitzgerald KA, Paludan SR. 2013. Proteasomal degradation of herpes simplex virus capsids in macrophages releases DNA to the cytosol for recognition by DNA sensors. J Immunol 190:2311-2319. https://doi.org/10.4049/jimmunol.1202749
12. Dell'Oste V, Gatti D, Gugliesi F, De Andrea M, Bawadekar M, Lo Cigno I, Biolatti M, Vallino M, Marschall M, Gariglio M, Landolfo S. 2014. Innate nuclear sensor IFI16 translocates into the cytoplasm during the early stage of in vitro human cytomegalovirus infection and is entrapped in the egressing virions during the late stage. J Virol 88:6970-6982. https:// doi.org/10.1128/JVI.00384-14
13. Diner BA, Lum KK, Toettcher JE, Cristea IM. 2016. Viral DNA sensors IFI16 and cyclic GMP-AMP synthase possess distinct functions in regulating viral gene expression, immune defenses, and apoptotic responses during herpesvirus infection. mBio 7:e01553-16. https://doi.org/10.1128/ mBio.01553-16
14. Orzalli MH, Knipe DM. 2014. Cellular sensing of viral DNA and viral evasion mechanisms. Annu Rev Microbiol 68:477-492. https://doi.org/ 10.1146/annurev-micro-091313-103409
15. Knipe DM. 2015. Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity. Virology 479-480: 153-159. https://doi.org/10.1016/j.virol.2015.02.009
16. Diner BA, Lum KK, Cristea IM. 2015. The emerging role of nuclear viral DNA sensors. J Biol Chem 290:26412-26421. https://doi.org/10.1074/jbc .R115.652289
17. Sun L, Wu J, Du F, Chen X, Chen ZJ. 2013. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339:786-791. https://doi.org/10.1126/science.1232458
18. Gao P, Ascano M, Wu Y, Barchet W, Gaffney BL, Zillinger T, Serganov AA, Liu Y, Jones RA, Hartmann G, Tuschl T, Patel DJ. 2013. Cyclic [G(2=,5=) pA(3=,5=)p] Is the metazoan second messenger produced by DNAactivated cyclic GMP-AMP synthase. Cell 153:1094-1107. https://doi.org/ 10.1016/j.cell.2013.04.046
19. Bhat N, Fitzgerald KA. 2014. Recognition of cytosolic DNA by cGAS and other STING-dependent sensors. Eur J Immunol 44:634-640. https://doi .org/10.1002/eji.201344127
20. Lio C-WJ, McDonald B, Takahashi M, Dhanwani R, Sharma N, Huang J, Pham E, Benedict CA, Sharma S. 2016. cGAS-STING signaling regulates initial innate control of cytomegalovirus infection. J Virol 90:7789-7797. https://doi.org/10.1128/JVI.01040-16
21. Paijo J, Döring M, Spanier J, Grabski E, Nooruzzaman M, Schmidt T, Witte G, Messerle M, Hornung V, Kaever V, Kalinke U. 2016. cGAS senses human cytomegalovirus and induces type I interferon responses in human monocyte-derived cells. PLoS Pathog 12:e1005546. https://doi .org/10.1371/journal.ppat.1005546
22. Burdette DL, Monroe KM, Sotelo-Troha K, Iwig JS, Eckert B, Hyodo M, Hayakawa Y, Vance RE. 2011. STING is a direct innate immune sensor of cyclic di-GMP. Nature 478:515-518. https://doi.org/10.1038/nature10429
23. Ishikawa H, Ma Z, Barber GN. 2009. STING regulates intracellular DNAmediated, type I interferon-dependent innate immunity. Nature 461: 788-792. https://doi.org/10.1038/nature08476
24. Christensen MH, Paludan SR. 2017. Viral evasion of DNA-stimulated innate immune responses. Cell Mol Immunol 14:4-13. https://doi.org/ 10.1038/cmi.2016.06
25. Ma Z, Damania B. 2016. The cGAS-STING defense pathway and its counteraction by viruses. Cell Host Microbe 19:150-158. https://doi.org/ 10.1016/j.chom.2016.01.010
26. Li T, Chen J, Cristea IM. 2013. Human cytomegalovirus tegument protein pUL83 inhibits IFI16-mediated DNA sensing for immune evasion. Cell Host Microbe 14:591-599. https://doi.org/10.1016/j.chom.2013.10.007
27. Wu J, Li W, Shao Y, Avey D, Fu B, Gillen J, Hand T, Ma S, Liu X, Miley W, Konrad A, Neipel F, Stürzl M, Whitby D, Li H, Zhu F. 2015. Inhibition of cGAS DNA sensing by a herpesvirus virion protein. Cell Host Microbe 18:333-344. https://doi.org/10.1016/j.chom.2015.07.015
28. Crow MS, Lum KK, Sheng X, Song B, Cristea IM. 2016. Diverse mechanisms evolved by DNA viruses to inhibit early host defenses. Crit Rev Biochem Mol Biol 51:452-481. https://doi.org/10.1080/10409238.2016 .1226250
29. Fu Y-Z, Su S, Gao Y-Q, Wang P-P, Huang Z-F, Hu M-M, Luo W-W, Li S, Luo M-H, Wang Y-Y, Shu H-B. 2017. Human cytomegalovirus tegument protein UL82 inhibits STING-mediated signaling to evade antiviral immunity. Cell Host Microbe 21:231-243. https://doi.org/10.1016/j.chom .2017.01.001
30. Su C, Zheng C. 2017. HerpeAEs cGAS/STING-mediated cytosolic DNAsensing pathway via its virion host shutoff protein UL41. J Virol 91: e02414-16. https://doi.org/10.1128/JVI.02414-16
31. Orzalli MH, DeLuca NA, Knipe DM. 2012. Nuclear IFI16 induction of IRF-3 signaling during herpesviral infection and degradation of IFI16 by the viral ICP0 protein. Proc Natl Acad Sci U S A 109:E3008-17. https://doi .org/10.1073/pnas.1211302109
32. Orzalli MH, Broekema NM, Knipe DM. 2016. Relative contributions of herpes simplex virus 1 ICP0 and vhs to loss of cellular IFI16 vary in different human cell types. J Virol 90:8351-8359. https://doi.org/10 .1128/JVI.00939-16
33. Christensen MH, Jensen SB, Miettinen JJ, Luecke S, Prabakaran T, Reinert LS, Mettenleiter T, Chen ZJ, Knipe DM, Sandri-Goldin RM, Enquist LW, Hartmann R, Mogensen TH, Rice SA, Nyman TA, Matikainen S, Paludan SR. 2016. HSV-1 ICP27 targets the TBK1-activated STING signalsome to inhibit virus-induced type I IFN expression. EMBO J 35:1385-1399. https://doi.org/10.15252/embj.201593458
34. Johnson KE, Song B, Knipe DM. 2008. Role for herpes simplex virus 1 ICP27 in the inhibition of type I interferon signaling. Virology 374: 487-494. https://doi.org/10.1016/j.virol.2008.01.001
35. Xing J, Ni L, Wang S, Wang K, Lin R, Zheng C. 2013. Herpes simplex virus 1-encoded tegument protein VP16 abrogates the production of beta interferon (IFN) by inhibiting NF-κB activation and blocking IFN regulatory factor 3 to recruit its coactivator CBP. J Virol 87:9788-9801. https:// doi.org/10.1128/JVI.01440-13
36. Abate DA, Watanabe S, Mocarski ES. 2004. Major human cytomegalovirus structural protein pp65 (ppUL83) prevents interferon response factor 3 activation in the interferon response. J Virol 78:10995-11006. https:// doi.org/10.1128/JVI.78.20.10995-11006.2004
37. Biolatti M, Dell'Oste V, Pautasso S, von Einem J, Marschall M, Plachter B, Gariglio M, De Andrea M, Landolfo S. 2016. Regulatory interaction between the cellular restriction factor IFI16 and viral pp65 (pUL83) AD IFI16 protein stability. J Virol 90:8238-8250. https://doi.org/10.1128/JVI .00923-16
38. Chevillotte M, Landwehr S, Linta L, Frascaroli G, Lüske A, Buser C, Mertens T, von Einem J. 2009. Major tegument protein pp65 of human cytomegalovirus is required for the incorporation of pUL69 and pUL97 into the virus particle and for viral growth in macrophages. J Virol 83:2480-2490. https://doi.org/10.1128/JVI.01818-08
39. Jønsson KL, Laustsen A, Krapp C, Skipper KA, Thavachelvam K, Hotter D, Egedal JH, Kjolby M, Mohammadi P, Prabakaran T, Sørensen LK, Sun C, Jensen SB, Holm CK, Lebbink RJ, Johannsen M, Nyegaard M, Mikkelsen JG, Kirchhoff F, Paludan SR, Jakobsen MR. 2017. IFI16 is required for DNA sensing in human macrophages by promoting production and function of cGAMP. Nat Commun 8:14391. https://doi.org/10.1038/ncomms14391
40. Rathinam VAK, Fitzgerald KA. 2011. Innate immune sensing of DNA viruses. Virology 411:153-162. https://doi.org/10.1016/j.virol.2011.02 .003
41. Thompson MR, Kaminski JJ, Kurt-Jones EA, Fitzgerald KA. 2011. Pattern recognition receptors and the innate immune response to viral infection. Viruses 3:920-940. https://doi.org/10.3390/v3060920
42. DeFilippis VR, Alvarado D, Sali T, Rothenburg S, Früh K. 2010. Human cytomegalovirus induces the interferon response via the DNA sensor ZBP1. J Virol 84:585-598. https://doi.org/10.1128/JVI.01748-09
43. Huang Y, Ma D, Huang H, Lu Y, Liao Y, Liu L, Liu X, Fang F. 2017. Interaction between HCMV pUL83 and human AIM2 disrupts the activation of the AIM2 inflammasome. Virol J 14:34. https://doi.org/10.1186/ s12985-016-0673-5
44. Huang Y, Liu L, Ma D, Liao Y, Lu Y, Huang H, Qin W, Liu X, Fang F. 2017. Human cytomegalovirus triggers the assembly of AIM2 inflammasome in THP-1-derived macrophages. J Med Virol 89:2188-2195. https://doi .org/10.1002/jmv.24846
45. Xia P, Wang S, Gao P, Gao G, Fan Z. 2016. DNA sensor cGAS-mediated immune recognition. Protein Cell 7:777-791. https://doi.org/10.1007/ s13238-016-0320-3
46. Almine JF, O'Hare CAJ, Dunphy G, Haga IR, Naik RJ, Atrih A, Connolly DJ, Taylor J, Kelsall IR, Bowie AG, Beard PM, Unterholzner L. 2017. IFI16 and cGAS cooperate in the activation of STING during DNA sensing in human keratinocytes. Nat Commun 8:14392. https://doi .org/10.1038/ncomms14392
47. Thompson MR, Sharma S, Atianand M, Jensen SB, Carpenter S, Knipe DM, Fitzgerald KA, Kurt-Jones EA. 2014. Interferon α-inducible protein (IFI) 16 transcriptionally regulates type I interferons and other interferonstimulated genes and controls the interferon response to both DNA and RNA viruses. J Biol Chem 289:23568-23581. https://doi.org/10.1074/jbc .M114.554147
48. Brinkman EK, Chen T, Amendola M, van Steensel B. 2014. Easy quantitative assessment of genome editing by sequence trace decomposition. Nucleic Acids Res 42:e168. https://doi.org/10.1093/nar/gku936
49. Gray EE, Winship D, Snyder JM, Child SJ, Geballe AP, Stetson DB. 2016. The AIM2-like receptors are dispensable for the interferon response to intracellular DNA. Immunity 45:255-266. https://doi.org/10.1016/j .immuni.2016.06.015
50. Orzalli MH, Broekema NM, Diner BA, Hancks DC, Elde NC, Cristea IM, Knipe DM. 2015. cGAS-mediated stabilization of IFI16 promotes innate signaling during herpes simplex virus infection. Proc Natl Acad Sci U S A 112:E1773-81. https://doi.org/10.1073/pnas.1424637112
51. Gao D, Wu J, Wu Y-T, Du F, Aroh C, Yan N, Sun L, Chen ZJ. 2013. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science 341:903-906. https://doi.org/10.1126/science.1240933
52. Liu Y, Li J, Chen J, Li Y, Wang W, Du X, Song W, Zhang W, Lin L, Yuan Z. 2015. Hepatitis B virus polymerase disrupts K63-AF STING to block innate cytosolic DNA-sensing pathways. J Virol 89:2287-2300. https://doi.org/ 10.1128/JVI.02760-14
53. Wang Y, Lian Q, Yang B, Yan S, Zhou H, He L, Lin G, Lian Z, Jiang Z, Sun B. 2015. TRIM30+ is a negative-feedback regulator of the intracellular DNA and DNA virus-triggered response by targeting STING. PLoS Pathog 11:e1005012. https://doi.org/10.1371/journal.ppat.1005012
54. Castillo Ramirez JA, Urcuqui-Inchima S. 2015. Dengue virus control of type I IFN responses: a history of manipulation and control. J Interferon Cytokine Res 35:421-430. https://doi.org/10.1089/jir.2014.0129
55. Kalamvoki M, Roizman B. 2014. HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the US3 protein kinase, and cell derivation. Proc Natl Acad Sci U S A 111:E611-17. https://doi.org/10 .1073/pnas.1323414111
56. Davis ME, Gack MU. 2015. Ubiquitination in the antiviral immune response. Virology 479-480:52-65. https://doi.org/10.1016/j.virol.2015.02 .033
57. Ablasser A. 2016. ReGLUation of cGAS. Nat Immunol 17:347-349. https:// doi.org/10.1038/ni.3397
58. Paludan SR. 2015. Activation and regulation of DNA-driven immune responses. Microbiol Mol Biol Rev 79:225-241. https://doi.org/10.1128/ MMBR.00061-14
59. Diner BA, Cristea IM. 2015. Blowing off steam: virus inhibition of cGAS DNA sensing. Cell Host Microbe 18:270-272. https://doi.org/10.1016/j .chom.2015.08.012
60. Chan YK, Gack MU. 2016. Viral evasion of intracellular DNA and RNA sensing. Nat Rev Microbiol 14:360-373. https://doi.org/10.1038/nrmicro .2016.45
61. Su C, Zhan G, Zheng C. 2016. Evasion of host antiviral innate immunity by HSV-1, an update. Virol J 13:38. https://doi.org/10.1186/s12985-016-0495-5
62. Dell'Oste V, Gatti D, Giorgio AG, Gariglio M, Landolfo S, De Andrea M. 2015. The interferon-inducible DNA-sensor protein IFI16: a key player in the antiviral response. New Microbiol 38:5-20
63. Landolfo S, De Andrea M, Dell'Oste V, Gugliesi F. 2016. Intrinsic host restriction factors of human cytomegalovirus replication and mechanisms of viral escape. World J Virol 5:87-96. https://doi.org/10.5501/wjv .v5.i3.87
64. Pignoloni B, Fionda C, Dell'Oste V, Luganini A, Cippitelli M, Zingoni A, Landolfo S, Gribaudo G, Santoni A, Cerboni C. 2016. Distinct roles for human cytomegalovirus immediate early proteins IE1 and IE2 in the transcriptional regulation of MICA and PVR/CD155 expression. J Immunol 197:4066-4078. https://doi.org/10.4049/jimmunol.1502527
65. Gariano GR, Dell'Oste V, Bronzini M, Gatti D, Luganini A, De Andrea M, Gribaudo G, Gariglio M, Landolfo S. 2012. The intracellular DNA sensor IFI16 gene acts as restriction factor for human cytomegalovirus replication. PLoS Pathog 8:e1002498. https://doi.org/10.1371/journal.ppat.1002498
66. Zhang Z, Evers DL, McCarville JF, Dantonel J-C, Huong S-M, Huang E-S. 2006. Evidence that the human cytomegalovirus IE2-86 protein binds mdm2 and facilitates mdm2 degradation. J Virol 80:3833-3843. https:// doi.org/10.1128/JVI.80.8.3833-3843.2006
67. Abe T, Barber GN. 2014. Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-κB activation through TBK1. J Virol 88:5328-5341. https://doi.org/10.1128/ JVI.00037-14
68. Chartier C, Degryse E, Gantzer M, Dieterle A, Pavirani A, Mehtali M. 1996. Efficient generation of recombinant adenovirus vectors by homologous recombination in Escherichia coli. J Virol 70:4805-4810
69. Gugliesi F, Mondini M, Ravera R, Robotti A, de Andrea M, Gribaudo G, Gariglio M, Landolfo S. 2005. Up-regulation of the interferon-inducible IFI16 gene by oxidative stress triggers p53 transcriptional activity in endothelial cells. J Leukoc Biol 77:820-829. https://doi.org/10.1189/jlb .0904507
70. Woodward JJ, Iavarone AT, Portnoy DA. 2010. c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response. Science 328:1703-1705. https://doi.org/10.1126/science.1189801