Advertisement

Us3 Protein Kinase Encoded by HSV: The Precise Function and Mechanism on Viral Life Cycle

  • Akihisa Kato
  • Yasushi Kawaguchi
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1045)

Abstract

All members of the Alphaherpesvirinae subfamily encode a serine/threonine kinase, designated Us3, which is not conserved in the other subfamilies. Us3 is a significant virulence factor for herpes simplex virus type 1 (HSV-1), which is one of the best-characterized members of the Alphaherpesvirinae family. Accumulating evidence indicates that HSV-1 Us3 is a multifunctional protein that plays various roles in the viral life cycle by phosphorylating a number of viral and cellular substrates. Therefore, the identification of Us3 substrates is directly connected to understanding Us3 functions and mechanisms. To date, more than 23 phosphorylation events upregulated by HSV-1 Us3 have been reported. However, few of these have been shown to be both physiological substrates of Us3 in infected cells and directly linked with Us3 functions in infected cells. In this chapter, we summarize the 12 physiological substrates of Us3 and the Us3-mediated functions. Furthermore, based on the identified phosphorylation sites of Us3 or Us3 homolog physiological substrates, we reverified consensus phosphorylation target sequences on the physiological substrates of Us3 and Us3 homologs in vitro and in infected cells. This information might aid the further identification of novel Us3 substrates and as yet unidentified Us3 functions.

Keywords

HSV Us3 Phosphorylation Protein kinase Consensus phosphorylation target sequence LOGO algorithm 

References

  1. Arend KC, Lenarcic EM, Vincent HA, Rashid N, Lazear E, McDonald IM, Gilbert TS, East MP, Herring LE, Johnson GL, Graves LM, Moorman NJ (2017) Kinome profiling identifies druggable targets for novel Human Cytomegalovirus (HCMV) antivirals. Mol Cell Proteomics 16(4 suppl 1):S263–S276.  https://doi.org/10.1074/mcp.M116.065375 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Arii J, Goto H, Suenaga T, Oyama M, Kozuka-Hata H, Imai T, Minowa A, Akashi H, Arase H, Kawaoka Y, Kawaguchi Y (2010) Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1. Nature 467(7317):859–862.  https://doi.org/10.1038/nature09420 CrossRefPubMedGoogle Scholar
  3. Benetti L, Roizman B (2004) Herpes simplex virus protein kinase US3 activates and functionally overlaps protein kinase A to block apoptosis. Proc Natl Acad Sci U S A 101(25):9411–9416.  https://doi.org/10.1073/pnas.0403160101 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Benetti L, Roizman B (2006) Protein kinase B/Akt is present in activated form throughout the entire replicative cycle of deltaU(S)3 mutant virus but only at early times after infection with wild-type herpes simplex virus 1. J Virol 80(7):3341–3348.  https://doi.org/10.1128/JVI.80.7.3341-3348.2006 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Benetti L, Munger J, Roizman B (2003) The herpes simplex virus 1 US3 protein kinase blocks caspase-dependent double cleavage and activation of the proapoptotic protein BAD. J Virol 77(11):6567–6573CrossRefPubMedPubMedCentralGoogle Scholar
  6. Bigalke JM, Heldwein EE (2017) Have NEC coat, will travel: structural basis of membrane budding during nuclear egress in herpesviruses. Adv Virus Res 97:107–141.  https://doi.org/10.1016/bs.aivir.2016.07.002 CrossRefPubMedGoogle Scholar
  7. Bigalke JM, Heuser T, Nicastro D, Heldwein EE (2014) Membrane deformation and scission by the HSV-1 nuclear egress complex. Nat Commun 5:4131.  https://doi.org/10.1038/ncomms5131 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Cartier A, Komai T, Masucci MG (2003) The Us3 protein kinase of herpes simplex virus 1 blocks apoptosis and induces phosphorylation of the Bcl-2 family member Bad. Exp Cell Res 291(1):242–250CrossRefPubMedGoogle Scholar
  9. Chuluunbaatar U, Roller R, Feldman ME, Brown S, Shokat KM, Mohr I (2010) Constitutive mTORC1 activation by a herpesvirus Akt surrogate stimulates mRNA translation and viral replication. Genes Dev 24(23):2627–2639.  https://doi.org/10.1101/gad.1978310 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Crooks GE, Hon G, Chandonia JM, Brenner SE (2004) WebLogo: a sequence logo generator. Genome Res 14(6):1188–1190.  https://doi.org/10.1101/gr.849004 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Deruelle MJ, Favoreel HW (2011) Keep it in the subfamily: the conserved alphaherpesvirus US3 protein kinase. J Gen Virol 92(Pt 1):18–30.  https://doi.org/10.1099/vir.0.025593-0 CrossRefPubMedGoogle Scholar
  12. Eaton HE, Saffran HA, Wu FW, Quach K, Smiley JR (2014) Herpes simplex virus protein kinases US3 and UL13 modulate VP11/12 phosphorylation, virion packaging, and phosphatidylinositol 3-kinase/Akt signaling activity. J Virol 88(13):7379–7388.  https://doi.org/10.1128/JVI.00712-14 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Frame MC, Purves FC, McGeoch DJ, Marsden HS, Leader DP (1987) Identification of the herpes simplex virus protein kinase as the product of viral gene US3. J Gen Virol 68(Pt 10):2699–2704.  https://doi.org/10.1099/0022-1317-68-10-2699 CrossRefPubMedGoogle Scholar
  14. Funk C, Ott M, Raschbichler V, Nagel CH, Binz A, Sodeik B, Bauerfeind R, Bailer SM (2015) The herpes simplex virus protein pUL31 escorts nucleocapsids to sites of nuclear egress, a process coordinated by its N-terminal domain. PLoS Pathog 11(6):e1004957.  https://doi.org/10.1371/journal.ppat.1004957 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Getz GS, Reardon CA (2017) Natural killer T cells in atherosclerosis. Nat Rev Cardiol 14(5):304–314.  https://doi.org/10.1038/nrcardio.2017.2 CrossRefPubMedGoogle Scholar
  16. Gingras AC, Gygi SP, Raught B, Polakiewicz RD, Abraham RT, Hoekstra MF, Aebersold R, Sonenberg N (1999) Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism. Genes Dev 13(11):1422–1437CrossRefPubMedPubMedCentralGoogle Scholar
  17. Hagen C, Dent KC, Zeev-Ben-Mordehai T, Grange M, Bosse JB, Whittle C, Klupp BG, Siebert CA, Vasishtan D, Bauerlein FJ, Cheleski J, Werner S, Guttmann P, Rehbein S, Henzler K, Demmerle J, Adler B, Koszinowski U, Schermelleh L, Schneider G, Enquist LW, Plitzko JM, Mettenleiter TC, Grunewald K (2015) Structural basis of vesicle formation at the inner nuclear membrane. Cell 163(7):1692–1701.  https://doi.org/10.1016/j.cell.2015.11.029 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Harr JC, Luperchio TR, Wong X, Cohen E, Wheelan SJ, Reddy KL (2015) Directed targeting of chromatin to the nuclear lamina is mediated by chromatin state and A-type lamins. J Cell Biol 208(1):33–52.  https://doi.org/10.1083/jcb.201405110 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Hirano Y, Segawa M, Ouchi FS, Yamakawa Y, Furukawa K, Takeyasu K, Horigome T (2005) Dissociation of emerin from barrier-to-autointegration factor is regulated through mitotic phosphorylation of emerin in a xenopus egg cell-free system. J Biol Chem 280(48):39925–39933.  https://doi.org/10.1074/jbc.M503214200 CrossRefPubMedGoogle Scholar
  20. Huang J, Manning BD (2009) A complex interplay between Akt, TSC2 and the two mTOR complexes. Biochem Soc Trans 37(Pt 1):217–222.  https://doi.org/10.1042/BST0370217 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Imai T, Sagou K, Arii J, Kawaguchi Y (2010) Effects of phosphorylation of herpes simplex virus 1 envelope glycoprotein B by Us3 kinase in vivo and in vitro. J Virol 84(1):153–162.  https://doi.org/10.1128/JVI.01447-09 CrossRefPubMedGoogle Scholar
  22. Imai T, Arii J, Minowa A, Kakimoto A, Koyanagi N, Kato A, Kawaguchi Y (2011) Role of the herpes simplex virus 1 Us3 kinase phosphorylation site and endocytosis motifs in the intracellular transport and neurovirulence of envelope glycoprotein B. J Virol 85(10):5003–5015.  https://doi.org/10.1128/JVI.02314-10 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Inoki K, Li Y, Zhu T, Wu J, Guan KL (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 4(9):648–657.  https://doi.org/10.1038/ncb839 CrossRefPubMedGoogle Scholar
  24. Jacob T, Van den Broeke C, Favoreel HW (2011) Viral serine/threonine protein kinases. J Virol 85(3):1158–1173.  https://doi.org/10.1128/JVI.01369-10 CrossRefPubMedGoogle Scholar
  25. Johnson DC, Baines JD (2011) Herpesviruses remodel host membranes for virus egress. Nat Rev Microbiol 9(5):382–394.  https://doi.org/10.1038/nrmicro2559 CrossRefPubMedGoogle Scholar
  26. Johnson LN, Noble ME, Owen DJ (1996) Active and inactive protein kinases: structural basis for regulation. Cell 85(2):149–158CrossRefPubMedPubMedCentralGoogle Scholar
  27. Katan M, Stevely WS, Leader DP (1985) Partial purification and characterization of a new phosphoprotein kinase from cells infected with pseudorabies virus. Eur J Biochem 152(1):57–65CrossRefPubMedGoogle Scholar
  28. Kato A, Yamamoto M, Ohno T, Kodaira H, Nishiyama Y, Kawaguchi Y (2005) Identification of proteins phosphorylated directly by the Us3 protein kinase encoded by herpes simplex virus 1. J Virol 79(14):9325–9331.  https://doi.org/10.1128/JVI.79.14.9325-9331.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Kato A, Tanaka M, Yamamoto M, Asai R, Sata T, Nishiyama Y, Kawaguchi Y (2008) Identification of a physiological phosphorylation site of the herpes simplex virus 1-encoded protein kinase Us3 which regulates its optimal catalytic activity in vitro and influences its function in infected cells. J Virol 82(13):6172–6189.  https://doi.org/10.1128/JVI.00044-08 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Kato A, Arii J, Shiratori I, Akashi H, Arase H, Kawaguchi Y (2009) Herpes simplex virus 1 protein kinase Us3 phosphorylates viral envelope glycoprotein B and regulates its expression on the cell surface. J Virol 83(1):250–261.  https://doi.org/10.1128/JVI.01451-08 CrossRefPubMedGoogle Scholar
  31. Kato A, Liu Z, Minowa A, Imai T, Tanaka M, Sugimoto K, Nishiyama Y, Arii J, Kawaguchi Y (2011) Herpes simplex virus 1 protein kinase Us3 and major tegument protein UL47 reciprocally regulate their subcellular localization in infected cells. J Virol 85(18):9599–9613.  https://doi.org/10.1128/JVI.00845-11 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kato A, Hirohata Y, Arii J, Kawaguchi Y (2014a) Phosphorylation of herpes simplex virus 1 dUTPase upregulated viral dUTPase activity to compensate for low cellular dUTPase activity for efficient viral replication. J Virol 88(14):7776–7785.  https://doi.org/10.1128/JVI.00603-14 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Kato A, Shindo K, Maruzuru Y, Kawaguchi Y (2014b) Phosphorylation of a herpes simplex virus 1 dUTPase by a viral protein kinase, Us3, dictates viral pathogenicity in the central nervous system but not at the periphery. J Virol 88(5):2775–2785.  https://doi.org/10.1128/JVI.03300-13 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Kato A, Tsuda S, Liu Z, Kozuka-Hata H, Oyama M, Kawaguchi Y (2014c) Herpes simplex virus 1 protein kinase Us3 phosphorylates viral dUTPase and regulates its catalytic activity in infected cells. J Virol 88(1):655–666.  https://doi.org/10.1128/JVI.02710-13 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kato A, Arii J, Koyanagi Y, Kawaguchi Y (2015) Phosphorylation of herpes simplex virus 1 dUTPase regulates viral virulence and genome integrity by compensating for low cellular dUTPase activity in the central nervous system. J Virol 89(1):241–248.  https://doi.org/10.1128/JVI.02497-14 CrossRefPubMedGoogle Scholar
  36. Kawaguchi Y, Kato K (2003) Protein kinases conserved in herpesviruses potentially share a function mimicking the cellular protein kinase cdc2. Rev Med Virol 13(5):331–340.  https://doi.org/10.1002/rmv.402 CrossRefPubMedGoogle Scholar
  37. Knighton DR, Zheng JH, Ten Eyck LF, Ashford VA, Xuong NH, Taylor SS, Sowadski JM (1991) Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science 253(5018):407–414CrossRefPubMedGoogle Scholar
  38. Kohl S, Strynadka NC, Hodges RS, Pereira L (1990) Analysis of the role of antibody-dependent cellular cytotoxic antibody activity in murine neonatal herpes simplex virus infection with antibodies to synthetic peptides of glycoprotein D and monoclonal antibodies to glycoprotein B. J Clin Invest 86(1):273–278.  https://doi.org/10.1172/JCI114695 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Leach N, Bjerke SL, Christensen DK, Bouchard JM, Mou F, Park R, Baines J, Haraguchi T, Roller RJ (2007) Emerin is hyperphosphorylated and redistributed in herpes simplex virus type 1-infected cells in a manner dependent on both UL34 and US3. J Virol 81(19):10792–10803.  https://doi.org/10.1128/JVI.00196-07 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Leader DP (1993) Viral protein kinases and protein phosphatases. Pharmacol Ther 59(3):343–389CrossRefPubMedGoogle Scholar
  41. Leader DP, Deana AD, Marchiori F, Purves FC, Pinna LA (1991) Further definition of the substrate specificity of the alpha-herpesvirus protein kinase and comparison with protein kinases A and C. Biochim Biophys Acta 1091(3):426–431CrossRefPubMedGoogle Scholar
  42. Leopardi R, Van Sant C, Roizman B (1997) The herpes simplex virus 1 protein kinase US3 is required for protection from apoptosis induced by the virus. Proc Natl Acad Sci U S A 94(15):7891–7896CrossRefPubMedPubMedCentralGoogle Scholar
  43. Liu Z, Kato A, Shindo K, Noda T, Sagara H, Kawaoka Y, Arii J, Kawaguchi Y (2014) Herpes simplex virus 1 UL47 interacts with viral nuclear egress factors UL31, UL34, and Us3 and regulates viral nuclear egress. J Virol 88(9):4657–4667.  https://doi.org/10.1128/JVI.00137-14 CrossRefPubMedPubMedCentralGoogle Scholar
  44. McGeoch DJ, Davison AJ (1986) Alphaherpesviruses possess a gene homologous to the protein kinase gene family of eukaryotes and retroviruses. Nucleic Acids Res 14(4):1765–1777CrossRefPubMedPubMedCentralGoogle Scholar
  45. Morimoto T, Arii J, Tanaka M, Sata T, Akashi H, Yamada M, Nishiyama Y, Uema M, Kawaguchi Y (2009) Differences in the regulatory and functional effects of the Us3 protein kinase activities of herpes simplex virus 1 and 2. J Virol 83(22):11624–11634.  https://doi.org/10.1128/JVI.00993-09 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Morris JB, Hofemeister H, O'Hare P (2007) Herpes simplex virus infection induces phosphorylation and delocalization of emerin, a key inner nuclear membrane protein. J Virol 81(9):4429–4437.  https://doi.org/10.1128/JVI.02354-06 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Mou F, Forest T, Baines JD (2007) US3 of herpes simplex virus type 1 encodes a promiscuous protein kinase that phosphorylates and alters localization of lamin A/C in infected cells. J Virol 81(12):6459–6470.  https://doi.org/10.1128/JVI.00380-07 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Mou F, Wills E, Baines JD (2009) Phosphorylation of the U(L)31 protein of herpes simplex virus 1 by the U(S)3-encoded kinase regulates localization of the nuclear envelopment complex and egress of nucleocapsids. J Virol 83(10):5181–5191.  https://doi.org/10.1128/JVI.00090-09 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Munger J, Roizman B (2001) The US3 protein kinase of herpes simplex virus 1 mediates the posttranslational modification of BAD and prevents BAD-induced programmed cell death in the absence of other viral proteins. Proc Natl Acad Sci U S A 98(18):10410–10415.  https://doi.org/10.1073/pnas.181344498 CrossRefPubMedPubMedCentralGoogle Scholar
  50. Naghavi MH, Gundersen GG, Walsh D (2013) Plus-end tracking proteins, CLASPs, and a viral Akt mimic regulate herpesvirus-induced stable microtubule formation and virus spread. Proc Natl Acad Sci U S A 110(45):18268–18273.  https://doi.org/10.1073/pnas.1310760110 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Niemi NM, MacKeigan JP (2013) Mitochondrial phosphorylation in apoptosis: flipping the death switch. Antioxid Redox Signal 19(6):572–582.  https://doi.org/10.1089/ars.2012.4982 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Nolen B, Taylor S, Ghosh G (2004) Regulation of protein kinases; controlling activity through activation segment conformation. Mol Cell 15(5):661–675.  https://doi.org/10.1016/j.molcel.2004.08.024 CrossRefPubMedGoogle Scholar
  53. Ogg PD, McDonell PJ, Ryckman BJ, Knudson CM, Roller RJ (2004) The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members. Virology 319(2):212–224.  https://doi.org/10.1016/j.virol.2003.10.019 CrossRefPubMedGoogle Scholar
  54. Poon AP, Roizman B (2005) Herpes simplex virus 1 ICP22 regulates the accumulation of a shorter mRNA and of a truncated US3 protein kinase that exhibits altered functions. J Virol 79(13):8470–8479.  https://doi.org/10.1128/JVI.79.13.8470-8479.2005 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 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(23):12671–12678CrossRefPubMedPubMedCentralGoogle Scholar
  56. 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(26):9993–9998.  https://doi.org/10.1073/pnas.0604142103 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Purves FC, Deana AD, Marchiori F, Leader DP, Pinna LA (1986) The substrate specificity of the protein kinase induced in cells infected with herpesviruses: studies with synthetic substrates [corrected] indicate structural requirements distinct from other protein kinases. Biochim Biophys Acta 889(2):208–215CrossRefPubMedGoogle Scholar
  58. Purves FC, Spector D, Roizman B (1991) The herpes simplex virus 1 protein kinase encoded by the US3 gene mediates posttranslational modification of the phosphoprotein encoded by the UL34 gene. J Virol 65(11):5757–5764PubMedPubMedCentralGoogle Scholar
  59. Rao P, Pham HT, Kulkarni A, Yang Y, Liu X, Knipe DM, Cresswell P, Yuan W (2011) Herpes simplex virus 1 glycoprotein B and US3 collaborate to inhibit CD1d antigen presentation and NKT cell function. J Virol 85(16):8093–8104.  https://doi.org/10.1128/JVI.02689-10 CrossRefPubMedPubMedCentralGoogle Scholar
  60. Reynolds AE, Ryckman BJ, Baines JD, Zhou Y, Liang L, Roller RJ (2001) U(L)31 and U(L)34 proteins of herpes simplex virus type 1 form a complex that accumulates at the nuclear rim and is required for envelopment of nucleocapsids. J Virol 75(18):8803–8817CrossRefPubMedPubMedCentralGoogle Scholar
  61. Reynolds AE, Wills EG, Roller RJ, Ryckman BJ, Baines JD (2002) Ultrastructural localization of the herpes simplex virus type 1 UL31, UL34, and US3 proteins suggests specific roles in primary envelopment and egress of nucleocapsids. J Virol 76(17):8939–8952CrossRefPubMedPubMedCentralGoogle Scholar
  62. Ryckman BJ, Roller RJ (2004) Herpes simplex virus type 1 primary envelopment: UL34 protein modification and the US3-UL34 catalytic relationship. J Virol 78(1):399–412CrossRefPubMedPubMedCentralGoogle Scholar
  63. Sagou K, Imai T, Sagara H, Uema M, Kawaguchi Y (2009) Regulation of the catalytic activity of herpes simplex virus 1 protein kinase Us3 by autophosphorylation and its role in pathogenesis. J Virol 83(11):5773–5783.  https://doi.org/10.1128/JVI.00103-09 CrossRefPubMedPubMedCentralGoogle Scholar
  64. Sen J, Liu X, Roller R, Knipe DM (2013) Herpes simplex virus US3 tegument protein inhibits Toll-like receptor 2 signaling at or before TRAF6 ubiquitination. Virology 439(2):65–73.  https://doi.org/10.1016/j.virol.2013.01.026 CrossRefPubMedGoogle Scholar
  65. Sloan DD, Zahariadis G, Posavad CM, Pate NT, Kussick SJ, Jerome KR (2003) CTL are inactivated by herpes simplex virus-infected cells expressing a viral protein kinase. J Immunol 171(12):6733–6741CrossRefPubMedGoogle Scholar
  66. Sugiyama N, Ishihama Y (2016) Large-scale profiling of protein kinases for cellular signaling studies by mass spectrometry and other techniques. J Pharm Biomed Anal 130:264–272.  https://doi.org/10.1016/j.jpba.2016.05.046 CrossRefPubMedGoogle Scholar
  67. Terry LJ, Vastag L, Rabinowitz JD, Shenk T (2012) Human kinome profiling identifies a requirement for AMP-activated protein kinase during human cytomegalovirus infection. Proc Natl Acad Sci U S A 109(8):3071–3076.  https://doi.org/10.1073/pnas.1200494109 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Vertessy BG, Toth J (2009) Keeping uracil out of DNA: physiological role, structure and catalytic mechanism of dUTPases. Acc Chem Res 42(1):97–106.  https://doi.org/10.1021/ar800114w CrossRefPubMedPubMedCentralGoogle Scholar
  69. Walters MS, Kinchington PR, Banfield BW, Silverstein S (2010) Hyperphosphorylation of histone deacetylase 2 by alphaherpesvirus US3 kinases. J Virol 84(19):9666–9676.  https://doi.org/10.1128/JVI.00981-10 CrossRefPubMedPubMedCentralGoogle Scholar
  70. Wang JT, Doong SL, Teng SC, Lee CP, Tsai CH, Chen MR (2009) Epstein-Barr virus BGLF4 kinase suppresses the interferon regulatory factor 3 signaling pathway. J Virol 83(4):1856–1869.  https://doi.org/10.1128/JVI.01099-08 CrossRefPubMedGoogle Scholar
  71. Wang X, Patenode C, Roizman B (2011) US3 protein kinase of HSV-1 cycles between the cytoplasm and nucleus and interacts with programmed cell death protein 4 (PDCD4) to block apoptosis. Proc Natl Acad Sci U S A 108(35):14632–14636.  https://doi.org/10.1073/pnas.1111942108 CrossRefPubMedPubMedCentralGoogle Scholar
  72. Wang S, Wang K, Lin R, Zheng C (2013) Herpes simplex virus 1 serine/threonine kinase US3 hyperphosphorylates IRF3 and inhibits beta interferon production. J Virol 87(23):12814–12827.  https://doi.org/10.1128/JVI.02355-13 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Wisner TW, Johnson DC (2004) Redistribution of cellular and herpes simplex virus proteins from the trans-golgi network to cell junctions without enveloped capsids. J Virol 78(21):11519–11535.  https://doi.org/10.1128/JVI.78.21.11519-11535.2004 CrossRefPubMedPubMedCentralGoogle Scholar
  74. Wisner TW, Wright CC, Kato A, Kawaguchi Y, Mou F, Baines JD, Roller RJ, Johnson DC (2009) Herpesvirus gB-induced fusion between the virion envelope and outer nuclear membrane during virus egress is regulated by the viral US3 kinase. J Virol 83(7):3115–3126.  https://doi.org/10.1128/JVI.01462-08 CrossRefPubMedPubMedCentralGoogle Scholar
  75. Xiong R, Rao P, Kim S, Li M, Wen X, Yuan W (2015) Herpes simplex virus 1 US3 phosphorylates cellular KIF3A to downregulate CD1d expression. J Virol 89(13):6646–6655.  https://doi.org/10.1128/JVI.00214-15 CrossRefPubMedPubMedCentralGoogle Scholar
  76. Yu X, He S (2016) The interplay between human herpes simplex virus infection and the apoptosis and necroptosis cell death pathways. Virol J 13:77.  https://doi.org/10.1186/s12985-016-0528-0 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Division of Molecular Virology, Department of Microbiology and ImmunologyThe Institute of Medical Science, The University of TokyoTokyoJapan
  2. 2.Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious DiseasesThe Institute of Medical Science, The University of TokyoTokyoJapan
  3. 3.Division of Molecular Virology, Department of Microbiology and ImmunologyThe Institute of Medical Science, The University of TokyoMinato-ku, TokyoJapan
  4. 4.Department of Infectious Disease Control, International Research Center for Infectious DiseasesThe Institute of Medical Science, The University of TokyoMinato-ku, TokyoJapan
  5. 5.Research Center for Asian Infectious DiseasesThe Institute of Medical Science, The University of TokyoMinato-ku, TokyoJapan

Personalised recommendations