Human cytomegalovirus pUL97 regulates the viral major immediate early promoter by phosphorylation-mediated disruption of histone deacetylase 1 binding

Journal of Virology

Volumn 87, Issue 13, 2013, Pages 7393-7408

  Bigley, Tarin M ^a   Reitsma, Justin M ^a   Mirza, Shama P ^a   Terhunea, Scott S ^a  

^a MEDICAL COLLEGE OF WISCONSIN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DAXX PROTEIN; HISTONE DEACETYLASE 1; HISTONE H3; LYSINE; PUL97 KINASE; UNCLASSIFIED DRUG; VIRUS PROTEIN;

ACETYLATION; ARTICLE; CHROMATIN; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME BINDING; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; ENZYME REGULATION; GENE DELETION; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; IMMEDIATE EARLY GENE; MASS SPECTROMETRY; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; TRANSACTIVATION; VIRUS GENOME;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; BENZIMIDAZOLES; BLOTTING, WESTERN; CHROMATIN IMMUNOPRECIPITATION; CYTOMEGALOVIRUS; DNA PRIMERS; FLUORESCENT ANTIBODY TECHNIQUE; GENE DELETION; GENE EXPRESSION REGULATION, VIRAL; HISTONE DEACETYLASE 1; HUMANS; IMMEDIATE-EARLY PROTEINS; IMMUNOPRECIPITATION; MASS SPECTROMETRY; MUTAGENESIS, SITE-DIRECTED; NUCLEAR PROTEINS; PHOSPHORYLATION; PROTEIN KINASES; RIBONUCLEOSIDES;

EID: 84880367640     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.02825-12     Document Type: Article

References (89)

1. Mocarski E, Pass TSRF. 2007 Cytomegaloviruses, p 2702-2772. In Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE (ed), Fields virology, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA
2. Hakki M, Chou S. 2011 The biology of cytomegalovirus drug resistance. Curr. Opin. Infect. Dis. 24:605-611.
3. Littler E, Stuart AD, Chee MS. 1992 Human cytomegalovirus UL97 open reading frame encodes a protein that phosphorylates the antiviral nucleoside analogue ganciclovir. Nature 358:160-162.
4. Sullivan V, Talarico CL, Stanat SC, Davis M, Coen DM, Biron KK. 1992. A protein kinase homologue controls phosphorylation of ganciclovir in human cytomegalovirus-infected cells. Nature 359:85.
5. van Zeijl M, Fairhurst J, Baum EZ, Sun L, Jones TR. 1997. The human cytomegalovirus UL97 protein is phosphorylated and a component of virions. Virology 231:72-80.
6. Wolf DG, Honigman A, Lazarovits J, Tavor E, Panet A. 1998. Characterization of the human cytomegalovirus UL97 gene product as a virionassociated protein kinase. Arch. Virol. 143:1223-1232.
7. Webel R, Milbradt J, Auerochs S, Schregel V, Held C, Nobauer K, Razzazi-Fazeli E, Jardin C, Wittenberg T, Sticht H, Marschall M. 2011. Two isoforms of the protein kinase pUL97 of human cytomegalovirus are differentially regulated in their nuclear translocation. J. Gen. Virol. 92: 638-649.
8. Webel R, Solbak SM, Held C, Milbradt J, Gross A, Eichler J, Wittenberg T, Jardin C, Sticht H, Fossen T, Marschall M. 2012. Nuclear import of isoforms of the cytomegalovirus kinase pUL97 is mediated by differential activity of NLS1 and NLS2 both acting through classical importin-alpha binding. J. Gen. Virol. 93:1756-1768.
9. Krosky PM, Baek MC, Coen DM. 2003. The human cytomegalovirus UL97 protein kinase, an antiviral drug target, is required at the stage of nuclear egress. J. Virol. 77:905-914.
10. Wolf DG, Courcelle CT, Prichard MN, Mocarski ES. 2001. Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation. Proc. Natl. Acad. Sci. U. S. A. 98:1895- 1900.
11. Baek MC, Krosky PM, Pearson A, Coen DM. 2004. Phosphorylation of the RNA polymerase II carboxyl-terminal domain in human cytomegalovirus-infected cells and in vitro by the viral UL97 protein kinase. Virology 324:184-193.
12. Hamirally S, Kamil JP, Ndassa-Colday YM, Lin AJ, Jahng WJ, Baek MC, Noton S, Silva LA, Simpson-Holley M, Knipe DM, Golan DE, Marto JA, Coen DM. 2009. Viral mimicry of Cdc2/cyclin-dependent kinase 1 mediates disruption of nuclear lamina during human cytomegalovirus nuclear egress. PLoS Pathog. 5:e1000275. doi:10.1371/journal.ppat.1000275
13. Hume AJ, Finkel JS, Kamil JP, Coen DM, Culbertson MR, Kalejta RF. 2008. Phosphorylation of retinoblastoma protein by viral protein with cyclin-dependent kinase function. Science 320:797-799.
14. Kawaguchi Y, Matsumura T, Roizman B, Hirai K. 1999. Cellular elongation factor 1delta is modified in cells infected with representative alpha-, beta-, or gammaherpesviruses. J. Virol. 73:4456-4460.
15. Krosky PM, Baek MC, Jahng WJ, Barrera I, Harvey RJ, Biron KK, Coen DM, Sethna PB. 2003. The human cytomegalovirus UL44 protein is a substrate for the UL97 protein kinase. J. Virol. 77:7720-7727.
16. Marschall M, Marzi A, aus dem Siepen P, Jochmann R, Kalmer M, Auerochs S, Lischka P, Leis M, Stamminger T. 2005. Cellular p32 recruits cytomegalovirus kinase pUL97 to redistribute the nuclear lamina. J. Biol. Chem. 280:33357-33367.
17. Milbradt J, Webel R, Auerochs S, Sticht H, Marschall M. 2010. Novel mode of phosphorylation-triggered reorganization of the nuclear lamina during nuclear egress of human cytomegalovirus. J. Biol. Chem. 285: 13979-13989.
18. Prichard MN, Sztul E, Daily SL, Perry AL, Frederick SL, Gill RB, Hartline CB, Streblow DN, Varnum SM, Smith RD, Kern ER. 2008. Human cytomegalovirus UL97 kinase activity is required for the hyperphosphorylation of retinoblastoma protein and inhibits the formation of nuclear aggresomes. J. Virol. 82:5054-5067.
19. Kamil JP, Hume AJ, Jurak I, Munger K, Kalejta RF, Coen DM. 2009. Human papillomavirus 16 E7 inactivator of retinoblastoma family proteins complements human cytomegalovirus lacking UL97 protein kinase. Proc. Natl. Acad. Sci. U. S. A. 106:16823-16828.
20. Kuny CV, Chinchilla K, Culbertson MR, Kalejta RF. 2010. Cyclindependent kinase-like function is shared by the beta- and gamma- subset of the conserved herpesvirus protein kinases. PLoS Pathog. 6:e1001092. doi:10.1371/journal.ppat.1001092
21. Prichard MN, Britt WJ, Daily SL, Hartline CB, Kern ER. 2005. Human cytomegalovirus UL97 kinase is required for the normal intranuclear distribution of pp65 and virion morphogenesis. J. Virol. 79:15494-15502.
22. Tower C, Fu L, Gill R, Prichard M, Lesort M, Sztul E. 2011. Human cytomegalovirus UL97 kinase prevents the deposition of mutant protein aggregates in cellular models of Huntington's disease and ataxia. Neurobiol. Dis. 41:11-22.
23. Azzeh M, Honigman A, Taraboulos A, Rouvinski A, Wolf DG. 2006. Structural changes in human cytomegalovirus cytoplasmic assembly sites in the absence of UL97 kinase activity. Virology 354:69-79.
24. Goldberg MD, Honigman A, Weinstein J, Chou S, Taraboulos A, Rouvinski A, Shinder V, Wolf DG. 2011. Human cytomegalovirus UL97 kinase and nonkinase functions mediate viral cytoplasmic secondary envelopment. J. Virol. 85:3375-3384.
25. Terhune SS, Moorman NJ, Cristea IM, Savaryn JP, Cuevas-Bennett C, Rout MP, Chait BT, Shenk T. 2010. Human cytomegalovirus UL29/28 protein interacts with components of the NuRD complex which promote accumulation of immediate-early RNA. PLoS Pathog. 6:e1000965. doi:10.1371/journal.ppat.1000965
26. Cunliffe VT. 2008. Eloquent silence: developmental functions of Class I histone deacetylases. Current Opin. Genet. Dev. 18:404-410.
27. Cuevas-Bennett C, Shenk T. 2008. Dynamic histone H3 acetylation and methylation at human cytomegalovirus promoters during replication in fibroblasts. J. Virol. 82:9525-9536.
28. Murphy JC, Fischle W, Verdin E, Sinclair JH. 2002. Control of cyto-megalovirus lytic gene expression by histone acetylation. EMBO J. 21: 1112-1120.
29. Nitzsche A, Paulus C, Nevels M. 2008. Temporal dynamics of cytomegalovirus chromatin assembly in productively infected human cells. J. Virol. 82:11167-11180.
30. Wright E, Bain M, Teague L, Murphy J, Sinclair J. 2005. Ets-2 repressor factor recruits histone deacetylase to silence human cytomegalovirus immediate-early gene expression in non-permissive cells. J. Gen. Virol. 86: 535-544.
31. Huang Y, Tang Q, Nguyen M, Dulal K, Wang W, Zhu H. 2011. Histone deacetylase 3, not histone deacetylase 2, interacts with the major immediate early locus of human cytomegalovirus. Virol. J. 8:151.
32. Saffert RT, Kalejta RF. 2006. 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. 80:3863-3871.
33. Li H, Leo C, Zhu J, Wu X, O'Neil J, Park EJ, Chen JD. 2000. Sequestration and inhibition of Daxx-mediated transcriptional repression by PML. Mol. Cell. Biol. 20:1784-1796.
34. Tang Q, Maul GG. 2003. Mouse cytomegalovirus immediate-early protein 1 binds with host cell repressors to relieve suppressive effects on viral transcription and replication during lytic infection. J. Virol. 77:1357- 1367.
35. Nevels M, Paulus C, Shenk T. 2004. Human cytomegalovirus immediate-early 1 protein facilitates viral replication by antagonizing histone deacetylation. Proc. Natl. Acad. Sci. U. S. A. 101:17234-17239.
36. Park JJ, Kim YE, Pham HT, Kim ET, Chung YH, Ahn JH. 2007. Functional interaction of the human cytomegalovirus IE2 protein with histone deacetylase 2 in infected human fibroblasts. J. Gen. Virol. 88: 3214-3223.
37. Reeves M, Murphy J, Greaves R, Fairley J, Brehm A, Sinclair J. 2006. Autorepression of the human cytomegalovirus major immediate-early promoter/enhancer at late times of infection is mediated by the recruitment of chromatin remodeling enzymes by IE86. J. Virol. 80:9998-10009.
38. Savaryn JP, Reitsma JM, Bigley TM, Halligan BD, Qian Z, Yu D, Terhune SS. 2013. Human cytomegalovirus pUL29/28 and pUL38 repression of p53-regulated p21CIP1 and caspase 1 promoters during infection. J. Virol. 87:2463-2474.
39. Poon AP, Liang Y, Roizman B. 2003. Herpes simplex virus 1 gene expression is accelerated by inhibitors of histone deacetylases in rabbit skin cells infected with a mutant carrying a cDNA copy of the infected-cell protein no. 0. J. Virol. 77:12671-12678.
40. Walters MS, Erazo A, Kinchington PR, Silverstein S. 2009. Histone deacetylases 1 and 2 are phosphorylated at novel sites during varicellazoster virus infection. J. Virol. 83:11502-11513.
41. Walters MS, Kinchington PR, Banfield BW, Silverstein S. 2010. Hyperphosphorylation of histone deacetylase 2 by alphaherpesvirus US3 kinases. J. Virol. 84:9666-9676.
42. Yu D, Smith GA, Enquist LW, Shenk T. 2002. Construction of a selfexcisable bacterial artificial chromosome containing the human cytomegalovirus genome and mutagenesis of the diploid TRL/IRL13 gene. J. Virol. 76:2316-2328.
43. Murphy E, Vanicek J, Robins H, Shenk T, Levine AJ. 2008. Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: implications for latency. Proc. Natl. Acad. Sci. U. S. A. 105:5453- 5458.
44. Warming S, Costantino N, Court DL, Jenkins NA, Copeland NG. 2005. Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res. 33:e36.
45. Yang WM, Yao YL, Sun JM, Davie JR, Seto E. 1997. Isolation and characterization of cDNAs corresponding to an additional member of the human histone deacetylase gene family. J. Biol. Chem. 272:28001-28007.
46. Terhune S, Torigoi E, Moorman N, Silva M, Qian Z, Shenk T, Yu D. 2007. Human cytomegalovirus UL38 protein blocks apoptosis. J. Virol. 81:3109-3123.
47. Zhu H, Shen Y, Shenk T. 1995. Human cytomegalovirus IE1 and IE2 proteins block apoptosis. J. Virol. 69:7960-7970.
48. Halligan BD, Greene AS. 2011. Visualize: a free and open source multifunction tool for proteomics data analysis. Proteomics 11:1058-1063.
49. Prichard MN. 2009. Function of human cytomegalovirus UL97 kinase in viral infection and its inhibition by maribavir. Rev. Med. Virol. 19:215- 229.
50. Biron KK, Harvey RJ, Chamberlain SC, Good SS, Smith AA, III, DavisMG, Talarico CL, Miller WH, Ferris R, Dornsife RE, Stanat SC, Drach JC, Townsend LB, Koszalka GW. 2002. Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action. Antimicrob. Agents Chemother. 46:2365-2372.
51. Chou S, Marousek GI. 2008. Accelerated evolution of maribavir resistance in a cytomegalovirus exonuclease domain II mutant. J. Virol. 82: 246-253.
52. Shannon-Lowe CD, Emery VC. 2010. The effects of maribavir on the autophosphorylation of ganciclovir resistant mutants of the cytomegalovirus UL97 protein. Herpesviridae 1:4. doi:10.1186/2042-4280-1-4
53. Reitsma JM, Savaryn JP, Faust K, Sato H, Halligan BD, Terhune SS. 2011. Antiviral inhibition targeting the HCMV kinase pUL97 requires pUL27-dependent degradation of Tip60 acetyltransferase and cell-cycle arrest. Cell Host Microbe 9:103-114.
54. Prichard MN, Gao N, Jairath S, Mulamba G, Krosky P, Coen DM, Parker BO, Pari GS. 1999. A recombinant human cytomegalovirus with a large deletion in UL97 has a severe replication deficiency. J. Virol. 73: 5663-5670.
55. Nowak B, Gmeiner A, Sarnow P, Levine AJ, Fleckenstein B. 1984. Physical mapping of human cytomegalovirus genes: identification of DNA sequences coding for a virion phosphoprotein of 71 kDa and a viral 65-kDa polypeptide. Virology 134:91-102.
56. Gilbert MJ, Riddell SR, Plachter B, Greenberg PD. 1996. Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product. Nature 383:720-722.
57. McLaughlin-Taylor E, Pande H, Forman SJ, Tanamachi B, Li CR, Zaia JA, Greenberg PD, Riddell SR. 1994. Identification of the major late human cytomegalovirus matrix protein pp65 as a target antigen for CD8_ virus-specific cytotoxic T lymphocytes. J. Med. Virol. 43:103-110.
58. Odeberg J, Plachter B, Branden L, Soderberg-Naucler C. 2003. Human cytomegalovirus protein pp65 mediates accumulation of HLA-DR in lysosomes and destruction of the HLA-DR alpha-chain. Blood 101:4870- 4877.
59. Schmolke S, Drescher P, Jahn G, Plachter B. 1995. Nuclear targeting of the tegument protein pp65 (UL83) of human cytomegalovirus: an unusual bipartite nuclear localization signal functions with other portions of the protein to mediate its efficient nuclear transport. J. Virol. 69:1071- 1078.
60. Chambers J, Angulo A, Amaratunga D, Guo H, Jiang Y, Wan JS, Bittner A, Frueh K, Jackson MR, Peterson PA, Erlander MG, Ghazal P. 1999. DNA microarrays of the complex human cytomegalovirus genome: profiling kinetic class with drug sensitivity of viral gene expression. J. Virol. 73:5757-5766.
61. Meier JL. 2001. Reactivation of the human cytomegalovirus major immediate-early regulatory region and viral replication in embryonal NTera2 cells: role of trichostatin A, retinoic acid, and deletion of the 21-base-pair repeats and modulator. J. Virol. 75:1581-1593.
62. Beckers T, Burkhardt C, Wieland H, Gimmnich P, Ciossek T, Maier T, Sanders K. 2007. Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group. Int. J. Cancer 121:1138-1148.
63. Alland L, Muhle R, Hou H, Jr, Potes J, Chin L, Schreiber-Agus N, DePinho RA. 1997. Role for N-CoR and histone deacetylase in Sin3-mediated transcriptional repression. Nature 387:49-55.
64. Hassig CA, Fleischer TC, Billin AN, Schreiber SL, Ayer DE. 1997. Histone deacetylase activity is required for full transcriptional repression by mSin3A. Cell 89:341-347.
65. Heinzel T, Lavinsky RM, Mullen TM, Soderstrom M, Laherty CD, Torchia J, Yang WM, Brard G, Ngo SD, Davie JR, Seto E, Eisenman RN, Rose DW, Glass CK, Rosenfeld MG. 1997. A complex containing NCoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature 387:43-48.
66. Laherty CD, Yang WM, Sun JM, Davie JR, Seto E, Eisenman RN. 1997. Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression. Cell 89:349-356.
67. Yang WM, Inouye C, Zeng Y, Bearss D, Seto E. 1996. Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator RPD3. Proc. Natl. Acad. Sci. U. S. A. 93: 12845-12850.
68. Nicolas E, Roumillac C, Trouche D. 2003. Balance between acetylation and methylation of histone H3 lysine 9 on the E2F-responsive dihydrofolate reductase promoter. Mol. Cell. Biol. 23:1614-1622.
69. Sengupta N, Seto E. 2004. Regulation of histone deacetylase activities. J. Cell. Biochem. 93:57-67.
70. Poon AP, Gu H, Roizman B. 2006. ICP0 and the US3 protein kinase of herpes simplex virus 1 independently block histone deacetylation to enable gene expression. Proc. Natl. Acad. Sci. U. S. A. 103:9993-9998.
71. Cai R, Kwon P, Yan-Neale Y, Sambuccetti L, Fischer D, Cohen D. 2001. Mammalian histone deacetylase 1 protein is posttranslationally modified by phosphorylation. Biochem. Biophys. Res. Commun. 283:445-453.
72. Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP. 2010. A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143:1174-1189.
73. Pflum MK, Tong JK, Lane WS, Schreiber SL. 2001. Histone deacetylase 1 phosphorylation promotes enzymatic activity and complex formation. J. Biol. Chem. 276:47733-47741.
74. Galasinski SC, Resing KA, Goodrich JA, Ahn NG. 2002. Phosphatase inhibition leads to histone deacetylases 1 and 2 phosphorylation and disruption of corepressor interactions. J. Biol. Chem. 277:19618-19626.
75. Karwowska-Desaulniers P, Ketko A, Kamath N, Pflum MK. 2007. Histone deacetylase 1 phosphorylation at S421 and S423 is constitutive in vivo, but dispensable in vitro. Biochem. Biophys. Res. Commun. 361: 349-355.
76. Pluemsampant S, Safronova OS, Nakahama K, Morita I. 2008. Protein kinase CK2 is a key activator of histone deacetylase in hypoxia-associated tumors. Int. J. Cancer 122:333-341.
77. Tsai SC, Seto E. 2002. Regulation of histone deacetylase 2 by protein kinase CK2. J. Biol. Chem. 277:31826-31833.
78. Mounce BC, Mboko WP, Bigley TM, Terhune SS, Tarakanova VL. 2013. A conserved gammaherpesvirus protein kinase targets histone deacetylases 1 and 2 to facilitate viral replication in primary macrophages. J. Virol. 87:7314-7325.
79. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ, Zhang H, Zha XM, Polakiewicz RD, Comb MJ. 2005. Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat. Biotechnol. 23:94-101.
80. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, MannM. 2006. Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127:635-648.
81. Wang B, Malik R, Nigg EA, Korner R. 2008. Evaluation of the lowspecificity protease elastase for large-scale phosphoproteome analysis. Anal. Chem. 80:9526-9533.
82. Ahn JH, Hayward GS. 1997. The major immediate-early proteins IE1 and IE2 of human cytomegalovirus colocalize with and disrupt PMLassociated nuclear bodies at very early times in infected permissive cells. J. Virol. 71:4599-4613.
83. Cristea IM, Moorman NJ, Terhune SS, Cuevas CD, O'Keefe ES, Rout MP, Chait BT, Shenk T. 2010. Human cytomegalovirus pUL83 stimulates activity of the viral immediate-early promoter through its interaction with the cellular IFI16 protein. J. Virol. 84:7803-7814.
84. Mitchell DP, Savaryn JP, Moorman NJ, Shenk T, Terhune SS. 2009. Human cytomegalovirus UL28 and UL29 open reading frames encode a spliced mRNA and stimulate accumulation of immediate-early RNAs. J. Virol. 83:10187-10197.
85. Liu Y, Biegalke BJ. 2002. The human cytomegalovirus UL35 gene encodes two proteins with different functions. J. Virol. 76:2460-2468.
86. Schierling K, Buser C, Mertens T, Winkler M. 2005. Human cytomegalovirus tegument protein ppUL35 is important for viral replication and particle formation. J. Virol. 79:3084-3096.
87. Lukashchuk V, McFarlane S, Everett RD, Preston CM. 2008. Human cytomegalovirus protein pp71 displaces the chromatin-associated factor ATRX from nuclear domain 10 at early stages of infection. J. Virol. 82: 12543-12554.
88. Ahn JH, Hayward GS. 2000. Disruption of PML-associated nuclear bodies by IE1 correlates with efficient early stages of viral gene expression and DNA replication in human cytomegalovirus infection. Virology 274: 39-55.
89. Korioth F, Maul GG, Plachter B, Stamminger T, Frey J. 1996. The nuclear domain 10 (ND10) is disrupted by the human cytomegalovirus gene product IE1. Exp. Cell Res. 229:155-158.