1887

Abstract

The regulation of the late viral gene expression in betaherpesviruses is largely undefined. We have previously shown that the murine cytomegalovirus proteins pM79 and pM92 are required for late gene transcription. Here, we provide insight into the mechanism of pM79 and pM92 activity by determining their interaction partners during infection. Co-immunoprecipitation-coupled MS studies demonstrate that pM79 and pM92 interact with an array of cellular and viral proteins involved in transcription. Specifically, we identify RNA polymerase II as a cellular target for both pM79 and pM92. We use inter-protein coevolution analysis to show how pM79 and pM92 likely assemble into a late transcription complex composed of late transcription regulators pM49, pM87 and pM95. Combining proteomic methods with coevolution computational analysis provides novel insights into the relationship between pM79, pM92 and RNA polymerase II and allows the generation of a model of the multi-component viral complex that regulates late gene transcription.

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2017-02-01
2020-01-23
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References

  1. Mocarski ES, Shenk T, Pass RF. (editors) Cytomegaloviruses Philadelphia: Lippincott Williams & Wilkins; 2007
    [Google Scholar]
  2. Pereyra F, Rubin RH. Prevention and treatment of cytomegalovirus infection in solid organ transplant recipients. Curr Opin Infect Dis 2004;17:357–361 [CrossRef][PubMed]
    [Google Scholar]
  3. Streblow DN, Orloff SL, Nelson JA. Acceleration of allograft failure by cytomegalovirus. Curr Opin Immunol 2007;19:577–582 [CrossRef][PubMed]
    [Google Scholar]
  4. Steininger C. Clinical relevance of cytomegalovirus infection in patients with disorders of the immune system. Clin Microbiol Infect 2007;13:953–963 [CrossRef][PubMed]
    [Google Scholar]
  5. Trincado DE, Scott GM, White PA, Hunt C, Rasmussen L et al. Human cytomegalovirus strains associated with congenital and perinatal infections. J Med Virol 2000;61:481–487[PubMed][CrossRef]
    [Google Scholar]
  6. Alford CA, Stagno S, Pass RF, Britt WJ. Congenital and perinatal cytomegalovirus infections. Rev Infect Dis 1990;12:S745–S753[PubMed][CrossRef]
    [Google Scholar]
  7. Grosse SD, Ross DS, Dollard SC. Congenital cytomegalovirus (CMV) infection as a cause of permanent bilateral hearing loss: a quantitative assessment. J Clin Virol 2008;41:57–62 [CrossRef][PubMed]
    [Google Scholar]
  8. Demmler GJ. Infectious Diseases Society of America and Centers for Disease Control. Summary of a workshop on surveillance for congenital cytomegalovirus disease. Rev Infect Dis 1991;13:315–329 [CrossRef][PubMed]
    [Google Scholar]
  9. Ornoy A, Diav-Citrin O. Fetal effects of primary and secondary cytomegalovirus infection in pregnancy. Reprod Toxicol 2006;21:399–409 [CrossRef][PubMed]
    [Google Scholar]
  10. Biron KK. Antiviral drugs for cytomegalovirus diseases. Antiviral Res 2006;71:154–163 [CrossRef][PubMed]
    [Google Scholar]
  11. Rawlinson WD, Farrell HE, Barrell BG. Analysis of the complete DNA sequence of murine cytomegalovirus. J Virol 1996;70:8833–8849[PubMed]
    [Google Scholar]
  12. Fitzgerald NA, Papadimitriou JM, Shellam GR. Cytomegalovirus-induced pneumonitis and myocarditis in newborn mice. A model for perinatal human cytomegalovirus infection. Arch Virol 1990;115:75–88[PubMed][CrossRef]
    [Google Scholar]
  13. Reddehase MJ, Simon CO, Seckert CK, Lemmermann N, Grzimek NK. Murine model of cytomegalovirus latency and reactivation. Curr Top Microbiol Immunol 2008;325:315–331[PubMed]
    [Google Scholar]
  14. Scalzo AA, Corbett AJ, Rawlinson WD, Scott GM, Degli-Esposti MA. The interplay between host and viral factors in shaping the outcome of cytomegalovirus infection. Immunol Cell Biol 2007;85:46–54 [CrossRef][PubMed]
    [Google Scholar]
  15. Omoto S, Mocarski ES. Transcription of true late (γ2) cytomegalovirus genes requires UL92 function that is conserved among beta- and gammaherpesviruses. J Virol 2014;88:120–130 [CrossRef][PubMed]
    [Google Scholar]
  16. Perng YC, Qian Z, Fehr AR, Xuan B, Yu D. The human cytomegalovirus gene UL79 is required for the accumulation of late viral transcripts. J Virol 2011;85:4841–4852 [CrossRef][PubMed]
    [Google Scholar]
  17. Isomura H, Stinski MF, Murata T, Yamashita Y, Kanda T et al. The human cytomegalovirus gene products essential for late viral gene expression assemble into prereplication complexes before viral DNA replication. J Virol 2011;85:6629–6644 [CrossRef][PubMed]
    [Google Scholar]
  18. Omoto S, Mocarski ES. Cytomegalovirus UL91 is essential for transcription of viral true late (γ2) genes. J Virol 2013;87:8651–8664 [CrossRef][PubMed]
    [Google Scholar]
  19. Aubry V, Mure F, Mariamé B, Deschamps T, Wyrwicz LS et al. Epstein–Barr virus late gene transcription depends on the assembly of a virus-specific preinitiation complex. J Virol 2014;88:12825–12838 [CrossRef][PubMed]
    [Google Scholar]
  20. Chapa TJ, Johnson LS, Affolter C, Valentine MC, Fehr AR et al. Murine cytomegalovirus protein pM79 is a key regulator for viral late transcription. J Virol 2013;87:9135–9147 [CrossRef][PubMed]
    [Google Scholar]
  21. Chapa TJ, Perng YC, French AR, Yu D. Murine cytomegalovirus protein pM92 is a conserved regulator of viral late gene expression. J Virol 2014;88:131–142 [CrossRef][PubMed]
    [Google Scholar]
  22. Nikolov DB, Burley SK. RNA polymerase II transcription initiation: a structural view. Proc Natl Acad Sci USA 1997;94:15–22[PubMed][CrossRef]
    [Google Scholar]
  23. Rice SA, Long MC, Lam V, Spencer CA. RNA polymerase II is aberrantly phosphorylated and localized to viral replication compartments following herpes simplex virus infection. J Virol 1994;68:988–1001[PubMed]
    [Google Scholar]
  24. Zhou C, Knipe DM. Association of herpes simplex virus type 1 ICP8 and ICP27 proteins with cellular RNA polymerase II holoenzyme. J Virol 2002;76:5893–5904 [CrossRef][PubMed]
    [Google Scholar]
  25. Taddeo B, Zhang W, Roizman B. Role of herpes simplex virus ICP27 in the degradation of mRNA by virion host shutoff RNase. J Virol 2010;84:10182–10190 [CrossRef][PubMed]
    [Google Scholar]
  26. Smith CA, Bates P, Rivera-Gonzalez R, Gu B, Deluca NA. ICP4, the major transcriptional regulatory protein of herpes simplex virus type 1, forms a tripartite complex with TATA-binding protein and TFIIB. J Virol 1993;67:4676–4687[PubMed]
    [Google Scholar]
  27. Kalamvoki M, Roizman B. The histone acetyltransferase CLOCK is an essential component of the herpes simplex virus 1 transcriptome that includes TFIID, ICP4, ICP27, and ICP22. J Virol 2011;85:9472–9477 [CrossRef][PubMed]
    [Google Scholar]
  28. Wagner LM, Lester JT, Sivrich FL, Deluca NA. The N terminus and C terminus of herpes simplex virus 1 ICP4 cooperate to activate viral gene expression. J Virol 2012;86:6862–6874 [CrossRef][PubMed]
    [Google Scholar]
  29. Bruce JW, Wilcox KW. Identification of a motif in the C terminus of herpes simplex virus regulatory protein ICP4 that contributes to activation of transcription. J Virol 2002;76:195–207[PubMed][CrossRef]
    [Google Scholar]
  30. Leopardi R, Ward PL, Ogle WO, Roizman B. Association of herpes simplex virus regulatory protein ICP22 with transcriptional complexes containing EAP, ICP4, RNA polymerase II, and viral DNA requires posttranslational modification by the U(L)13 proteinkinase. J Virol 1997;71:1133–1139[PubMed]
    [Google Scholar]
  31. Fraser KA, Rice SA. Herpes simplex virus immediate-early protein ICP22 triggers loss of serine 2-phosphorylated RNA polymerase II. J Virol 2007;81:5091–5101 [CrossRef][PubMed]
    [Google Scholar]
  32. Wu TT, Park T, Kim H, Tran T, Tong L et al. ORF30 and ORF34 are essential for expression of late genes in murine gammaherpesvirus 68. J Virol 2009;83:2265–2273 [CrossRef][PubMed]
    [Google Scholar]
  33. Davis ZH, Verschueren E, Jang GM, Kleffman K, Johnson JR et al. Global mapping of herpesvirus–host protein complexes reveals a transcription strategy for late genes. Mol Cell 2015;57:349–360 [CrossRef][PubMed]
    [Google Scholar]
  34. Perng YC, Campbell JA, Lenschow DJ, Yu D. Human cytomegalovirus pUL79 is an elongation factor of RNA polymerase II for viral gene transcription. PLoS Pathog 2014;10:e1004350 [CrossRef][PubMed]
    [Google Scholar]
  35. Harvey DM, Levine AJ. p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts. Genes Dev 1991;5:2375–2385[PubMed][CrossRef]
    [Google Scholar]
  36. Dunn W, Chou C, Li H, Hai R, Patterson D et al. Functional profiling of a human cytomegalovirus genome. Proc Natl Acad Sci USA 2003;100:14223–14228 [CrossRef][PubMed]
    [Google Scholar]
  37. Wyrwicz LS, Rychlewski L. Identification of Herpes TATT-binding protein. Antiviral Res 2007;75:167–172 [CrossRef][PubMed]
    [Google Scholar]
  38. Davis ZH, Hesser CR, Park J, Glaunsinger BA. Interaction between ORF24 and ORF34 in the Kaposi's sarcoma-associated herpesvirus late gene transcription factor complex is essential for viral late gene expression. J Virol 2015;90:599–604 [CrossRef][PubMed]
    [Google Scholar]
  39. Ochoa D, Juan D, Valencia A, Pazos F. Detection of significant protein coevolution. Bioinformatics 2015;31:2166–2173 [CrossRef][PubMed]
    [Google Scholar]
  40. Zhou H, Jakobsson E. Predicting protein–protein interaction by the mirrortree method: possibilities and limitations. PLoS One 2013;8:e81100 [CrossRef][PubMed]
    [Google Scholar]
  41. Ochoa D, Pazos F. Studying the co-evolution of protein families with the Mirrortree web server. Bioinformatics 2010;26:1370–1371 [CrossRef][PubMed]
    [Google Scholar]
  42. Kann MG, Shoemaker BA, Panchenko AR, Przytycka TM. Correlated evolution of interacting proteins: looking behind the mirrortree. J Mol Biol 2009;385:91–98 [CrossRef][PubMed]
    [Google Scholar]
  43. Kamisetty H, Ovchinnikov S, Baker D. Assessing the utility of coevolution-based residue–residue contact predictions in a sequence- and structure-rich era. Proc Natl Acad Sci USA 2013;110:15674–15679 [CrossRef][PubMed]
    [Google Scholar]
  44. Kann MG, Jothi R, Cherukuri PF, Przytycka TM. Predicting protein domain interactions from coevolution of conserved regions. Proteins 2007;67:811–820 [CrossRef][PubMed]
    [Google Scholar]
  45. Esmaielbeiki R, Krawczyk K, Knapp B, Nebel JC, Deane CM. Progress and challenges in predicting protein interfaces. Brief Bioinform 2016;17:117–131 [CrossRef][PubMed]
    [Google Scholar]
  46. Brulois K, Wong LY, Lee HR, Sivadas P, Ensser A et al. Association of Kaposi's sarcoma-associated herpesvirus ORF31 with ORF34 and ORF24 is critical for late gene expression. J Virol 2015;89:6148–6154 [CrossRef][PubMed]
    [Google Scholar]
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