Cellular serine/threonine phosphatase activity during human cytomegalovirus infection

Virology

Volumn 380, Issue 2, 2008, Pages 255-263

  Hakki, Morgan ^a,b   Geballe, Adam P ^a,b  

^a USA   (United States)

^b UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Cytomegalovirus; Phosphatase

Indexed keywords

CALYCULIN A; EUKARYOTIC TRANSLATION INITIATION FACTOR 2ALPHA; INITIATION FACTOR 2; OKADAIC ACID; PHOSPHATASE; PHOSPHOPROTEIN PHOSPHATASE 1; PROTEIN PHOSPHATASES 2A; SERINE; THREONINE; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; CYTOMEGALOVIRUS INFECTION; DRUG EFFECT; EMBRYO; ENZYME ACTIVITY; EXPERIMENT; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS;

ANIMALS; CELLS, CULTURED; CYTOMEGALOVIRUS INFECTIONS; EIF-2 KINASE; ENZYME INHIBITORS; EUKARYOTIC INITIATION FACTOR-2; HUMANS; MICE; OKADAIC ACID; OXAZOLES; PHOSPHOPROTEIN PHOSPHATASES; PHOSPHORYLATION; PROTEIN BIOSYNTHESIS;

CYTOMEGALOVIRUS; HUMAN HERPESVIRUS 5;

EID: 53249151598     PISSN: 00426822     EISSN: 10960341     Source Type: Journal    
DOI: 10.1016/j.virol.2008.07.028     Document Type: Article

References (87)

1. Alderete J.P., Child S.J., and Geballe A.P. Abundant early expression of gpUL4 from a human cytomegalovirus mutant lacking a repressive upstream open reading frame. J. Virol. 75 15 (2001) 7188-7192
2. Baek M.C., Krosky P.M., He Z., and Coen D.M. Specific phosphorylation of exogenous protein and peptide substrates by the human cytomegalovirus UL97 protein kinase. Importance of the P+5 position. J. Biol. Chem. 277 33 (2002) 29593-29599
3. Baek M.C., Krosky P.M., Pearson A., and Coen D.M. 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 1 (2004) 184-193
4. Baharians Z., and Schonthal A.H. Autoregulation of protein phosphatase type 2A expression. J. Biol. Chem. 273 30 (1998) 19019-19024
5. Barrasa M.I., Harel N.Y., and Alwine J.C. The phosphorylation status of the serine-rich region of the human cytomegalovirus 86-kilodalton major immediate-early protein IE2/IEP86 affects temporal viral gene expression. J. Virol. 79 3 (2005) 1428-1437
6. Bollen M. Combinatorial control of protein phosphatase-1. Trends Biochem. Sci. 26 7 (2001) 426-431
7. Bresnahan W.A., Boldogh I., Chi P., Thompson E.A., and Albrecht T. Inhibition of cellular Cdk2 activity blocks human cytomegalovirus replication. Virology 231 2 (1997) 239-247
8. Brush M.H., Weiser D.C., and Shenolikar S. Growth arrest and DNA damage-inducible protein GADD34 targets protein phosphatase 1 alpha to the endoplasmic reticulum and promotes dephosphorylation of the alpha subunit of eukaryotic translation initiation factor 2. Mol. Cell. Biol. 23 4 (2003) 1292-1303
9. Bryant J.C., Westphal R.S., and Wadzinski B.E. Methylated C-terminal leucine residue of PP2A catalytic subunit is important for binding of regulatory Balpha subunit. Biochem. J. 339 Pt 2 (1999) 241-246
10. Chambers J., Angulo A., Amaratunga D., Guo H., Jiang Y., Wan J.S., Bittner A., Frueh K., Jackson M.R., Peterson P.A., Erlander M.G., and Ghazal P. DNA microarrays of the complex human cytomegalovirus genome: profiling kinetic class with drug sensitivity of viral gene expression. J. Virol. 73 7 (1999) 5757-5766
11. Chan Y.J., Tseng W.P., and Hayward G.S. Two distinct upstream regulatory domains containing multicopy cellular transcription factor binding sites provide basal repression and inducible enhancer characteristics to the immediate-early IES (US3) promoter from human cytomegalovirus. J. Virol. 70 8 (1996) 5312-5328
12. Chen S.C., Kramer G., and Hardesty B. Isolation and partial characterization of an Mr 60,000 subunit of a type 2A phosphatase from rabbit reticulocytes. J. Biol. Chem. 264 13 (1989) 7267-7275
13. Chen J., Martin B.L., and Brautigan D.L. Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation. Science 257 5074 (1992) 1261-1264
14. Child S.J., Jarrahian S., Harper V.M., and Geballe A.P. Complementation of vaccinia virus lacking the double-stranded RNA-binding protein gene E3L by human cytomegalovirus. J. Virol. 76 10 (2002) 4912-4918
15. Child S.J., Hakki M., De Niro K.L., and Geballe A.P. Evasion of cellular antiviral responses by human cytomegalovirus TRS1 and IRS1. J. Virol. 78 1 (2004) 197-205
16. Chou J., Kern E.R., Whitley R.J., and Roizman B. Mapping of herpes simplex virus-1 neurovirulence to gamma 134.5, a gene nonessential for growth in culture. Science 250 4985 (1990) 1262-1266
17. Cohen P.T. Protein phosphatase 1-targeted in many directions. J. Cell. Sci. 115 Pt 2 (2002) 241-256
18. Connor J.H., Weiser D.C., Li S., Hallenbeck J.M., and Shenolikar S. Growth arrest and DNA damage-inducible protein GADD34 assembles a novel signaling complex containing protein phosphatase 1 and inhibitor 1. Mol. Cell. Biol. 21 20 (2001) 6841-6850
19. Damuni Z., Xiong H., and Li M. Autophosphorylation-activated protein kinase inactivates the protein tyrosine phosphatase activity of protein phosphatase 2A. FEBS Lett. 352 3 (1994) 311-314
20. DeGracia D.J., Sullivan J.M., Neumar R.W., Alousi S.S., Hikade K.R., Pittman J.E., White B.C., Rafols J.A., and Krause G.S. Effect of brain ischemia and reperfusion on the localization of phosphorylated eukaryotic initiation factor 2 alpha. J. Cereb. Blood Flow. Metab. 17 12 (1997) 1291-1302
21. Dever T.E., Dar A.C., and Sicheri F. The eIF2alpha kinases. In: Mathews M.B., Sonenberg N., and Hershey J.W.B. (Eds). Translational Control in Biology and Medicine (2007), Cold Spring Harbor Laboratory Press 319-344
22. Ernst V., Levin D.H., Foulkes J.G., and London I.M. Effects of skeletal muscle protein phosphatase inhibitor-2 on protein synthesis and protein phosphorylation in rabbit reticulocyte lysates. Proc. Natl. Acad. Sci. U. S. A. 79 23 (1982) 7092-7096
23. Favre B., Zolnierowicz S., Turowski P., and Hemmings B.A. The catalytic subunit of protein phosphatase 2A is carboxyl-methylated in vivo. J. Biol. Chem. 269 23 (1994) 16311-16317
24. Favre B., Turowski P., and Hemmings B.A. Differential inhibition and posttranslational modification of protein phosphatase 1 and 2A in MCF7 cells treated with calyculin-A, okadaic acid, and tautomycin. J. Biol. Chem. 272 21 (1997) 13856-13863
25. Fish K.N., Soderberg-Naucler C., and Nelson J.A. Steady-state plasma membrane expression of human cytomegalovirus gB is determined by the phosphorylation state of Ser900. J. Virol. 72 8 (1998) 6657-6664
26. Fladmark K.E., Brustugun O.T., Hovland R., Boe R., Gjertsen B.T., Zhivotovsky B., and Doskeland S.O. Ultrarapid caspase-3 dependent apoptosis induction by serine/threonine phosphatase inhibitors. Cell. Death Differ. 6 11 (1999) 1099-1108
27. Flores-Delgado G., Liu C.W., Sposto R., and Berndt N. A limited screen for protein interactions reveals new roles for protein phosphatase 1 in cell cycle control and apoptosis. J. Proteome Res. 6 3 (2007) 1165-1175
28. Fortunato E.A., McElroy A.K., Sanchez I., and Spector D.H. Exploitation of cellular signaling and regulatory pathways by human cytomegalovirus. Trends Microbiol. 8 3 (2000) 111-119
29. Geballe A.P., and Mocarski E.S. Translational control of cytomegalovirus gene expression is mediated by upstream AUG codons. J. Virol. 62 9 (1988) 3334-3340
30. Gjertsen B.T., and Doskeland S.O. Protein phosphorylation in apoptosis. Biochim. Biophys. Acta 1269 2 (1995) 187-199
31. Gjertsen B.T., Cressey L.I., Ruchaud S., Houge G., Lanotte M., and Doskeland S.O. Multiple apoptotic death types triggered through activation of separate pathways by cAMP and inhibitors of protein phosphatases in one (IPC leukemia) cell line. J. Cell. Sci. 107 Pt 12 (1994) 3363-3377
32. Guan L., Song K., Pysz M.A., Curry K.J., Hizli A.A., Danielpour D., Black A.R., and Black J.D. Protein kinase C-mediated down-regulation of cyclin D1 involves activation of the translational repressor 4E-BP1 via a phosphoinositide 3-kinase/Akt-independent, protein phosphatase 2A-dependent mechanism in intestinal epithelial cells. J. Biol. Chem. 282 19 (2007) 14213-14225
33. Gupta V., Ogawa A.K., Du X., Houk K.N., and Armstrong R.W. A model for binding of structurally diverse natural product inhibitors of protein phosphatases PP1 and PP2A. J. Med. Chem. 40 20 (1997) 3199-3206
34. Hakki M., Marshall E.E., De Niro K.L., and Geballe A.P. Binding and nuclear relocalization of protein kinase R by human cytomegalovirus TRS1. J. Virol. 80 23 (2006) 11817-11826
35. Harel N.Y., and Alwine J.C. Phosphorylation of the human cytomegalovirus 86-kilodalton immediate-early protein IE2. J. Virol. 72 7 (1998) 5481-5492
36. He B., Gross M., and Roizman B. The gamma(1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc. Natl. Acad. Sci. U. S. A. 94 3 (1997) 843-848
37. Helps N.R., Luo X., Barker H.M., and Cohen P.T. NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1. Biochem. J. 349 Pt 2 (2000) 509-518
38. Hertel L., and Mocarski E.S. Global analysis of host cell gene expression late during cytomegalovirus infection reveals extensive dysregulation of cell cycle gene expression and induction of Pseudomitosis independent of US28 function. J. Virol. 78 21 (2004) 11988-12011
39. Hertel L., Chou S., and Mocarski E.S. Viral and cell cycle-regulated kinases in cytomegalovirus-induced pseudomitosis and replication. PLoS Pathog. 3 1 (2007) e6
40. Hume A.J., Finkel J.S., Kamil J.P., Coen D.M., Culbertson M.R., and Kalejta R.F. Phosphorylation of retinoblastoma protein by viral protein with cyclin-dependent kinase function. Science 320 5877 (2008) 797-799
41. Ishihara H., Martin B.L., Brautigan D.L., Karaki H., Ozaki H., Kato Y., Fusetani N., Watabe S., Hashimoto K., Uemura D., et al. Calyculin A and okadaic acid: inhibitors of protein phosphatase activity. Biochem. Biophys. Res. Commun. 159 3 (1989) 871-877
42. Isler J.A., Skalet A.H., and Alwine J.C. Human cytomegalovirus infection activates and regulates the unfolded protein response. J. Virol. 79 11 (2005) 6890-6899
43. Janssens V., and Goris J. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem. J. 353 Pt 3 (2001) 417-439
44. Jarvis M.A., Jones T.R., Drummond D.D., Smith P.P., Britt W.J., Nelson J.A., and Baldick C.J. Phosphorylation of human cytomegalovirus glycoprotein B (gB) at the acidic cluster casein kinase 2 site (Ser900) is required for localization of gB to the trans-Golgi network and efficient virus replication. J. Virol. 78 1 (2004) 285-293
45. Jault F.M., Jault J.M., Ruchti F., Fortunato E.A., Clark C., Corbeil J., Richman D.D., and Spector D.H. Cytomegalovirus infection induces high levels of cyclins, phosphorylated Rb, and p53, leading to cell cycle arrest. J. Virol. 69 11 (1995) 6697-6704
46. Jiang H.Y., Wek S.A., McGrath B.C., Scheuner D., Kaufman R.J., Cavener D.R., and Wek R.C. Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 is required for activation of NF-kappaB in response to diverse cellular stresses. Mol. Cell. Biol. 23 16 (2003) 5651-5663
47. Jousse C., Oyadomari S., Novoa I., Lu P., Zhang Y., Harding H.P., and Ron D. Inhibition of a constitutive translation initiation factor 2alpha phosphatase, CReP, promotes survival of stressed cells. J. Cell. Biol. 163 4 (2003) 767-775
48. Kazemi S., Papadopoulou S., Li S., Su Q., Wang S., Yoshimura A., Matlashewski G., Dever T.E., and Koromilas A.E. Control of alpha subunit of eukaryotic translation initiation factor 2 (eIF2 alpha) phosphorylation by the human papillomavirus type 18 E6 oncoprotein: implications for eIF2 alpha-dependent gene expression and cell death. Mol. Cell. Biol. 24 8 (2004) 3415-3429
49. Keay S., and Baldwin B.R. Evidence for the role of cell protein phosphorylation in human cytomegalovirus/host cell fusion. J. Gen. Virol. 77 Pt 10 (1996) 2597-2604
50. Latreille M., and Larose L. Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress. J. Biol. Chem. 281 36 (2006) 26633-26644
51. Longin S., Zwaenepoel K., Louis J.V., Dilworth S., Goris J., and Janssens V. Selection of protein phosphatase 2A regulatory subunits is mediated by the C terminus of the catalytic subunit. J. Biol. Chem. 282 37 (2007) 26971-26980
52. Longin S., Zwaenepoel K., Martens E., Louis J.V., Rondelez E., Goris J., and Janssens V. Spatial control of protein phosphatase 2A (de)methylation. Exp. Cell. Res. 314 1 (2008) 68-81
53. Mantovani F., and Banks L. The human papillomavirus E6 protein and its contribution to malignant progression. Oncogene 20 54 (2001) 7874-7887
54. Margolis S.S., and Kornbluth S. When the checkpoints have gone: insights into Cdc25 functional activation. Cell. Cycle 3 4 (2004) 425-428
55. Margolis S.S., Perry J.A., Weitzel D.H., Freel C.D., Yoshida M., Haystead T.A., and Kornbluth S. A role for PP1 in the Cdc2/Cyclin B-mediated positive feedback activation of Cdc25. Mol. Biol. Cell. 17 4 (2006) 1779-1789
56. Margolis S.S., Walsh S., Weiser D.C., Yoshida M., Shenolikar S., and Kornbluth S. PP1 control of M phase entry exerted through 14-3-3-regulated Cdc25 dephosphorylation. EMBO J. 22 21 (2003) 5734-5745
57. Michelson S., Turowski P., Picard L., Goris J., Landini M.P., Topilko A., Hemmings B., Bessia C., Garcia A., and Virelizier J.L. Human cytomegalovirus carries serine/threonine protein phosphatases PP1 and a host-cell derived PP2A. J. Virol. 70 3 (1996) 1415-1423
58. Mocarski, E.S., Shenk, T., Pass, R.F., 2007. Cytomegaloviruses. In: Knipe, D.M. Howley, P.M. (Eds.), Fields Virology, 5th ed., Vol. 2, pp. 2701-2772. 2 vols. Lippincott Williams and Wilkins, Philadelphia.
59. Morimoto H., Okamura H., Yoshida K., Kitamura S., and Haneji T. Okadaic acid induces apoptosis through double-stranded RNA-dependent protein kinase/eukaryotic initiation factor-2alpha pathway in human osteoblastic MG63 cells. J. Biochem. (Tokyo) 136 4 (2004) 433-438
60. Morimoto H., Ozaki A., Okamura H., Yoshida K., Kitamura S., and Haneji T. Okadaic acid induces tyrosine phosphorylation of IkappaBalpha that mediated by PKR pathway in human osteoblastic MG63 cells. Mol. Cell. Biochem. 276 1-2 (2005) 211-217
61. Nakamura K., Koda T., Kakinuma M., Matsuzawa S., Kitamura K., Mizuno Y., and Kikuchi K. Cell cycle dependent gene expressions and activities of protein phosphatases PP1 and PP2A in mouse NIH3T3 fibroblasts. Biochem. Biophys. Res. Commun. 187 1 (1992) 507-514
62. Nishikawa M., Omay S.B., Toyoda H., Tawara I., Shima H., Nagao M., Hemmings B.A., Mumby M.C., and Deguchi K. Expression of the catalytic and regulatory subunits of protein phosphatase type 2A may be differentially modulated during retinoic acid-induced granulocytic differentiation of HL-60 cells. Cancer Res. 54 18 (1994) 4879-4884
63. Novoa I., Zeng H., Harding H.P., and Ron D. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J. Cell. Biol. 153 5 (2001) 1011-1022
64. Pande H., Lee T.D., Churchill M.A., and Zaia J.A. Structural analysis of a 64-kDa major structural protein of human cytomegalovirus (Towne): identification of a phosphorylation site and comparison to pp65 of HCMV (AD169). Virology 178 1 (1990) 6-14
65. Petryshyn R., Levin D.H., and London I.M. Regulation of double-stranded RNA-activated eukaryotic initiation factor 2 alpha kinase by type 2 protein phosphatase in reticulocyte lysates. Proc. Natl. Acad. Sci. U. S. A. 79 21 (1982) 6512-6516
66. Prichard M.N., Gao N., Jairath S., Mulamba G., Krosky P., Coen D.M., Parker B.O., and Pari G.S. A recombinant human cytomegalovirus with a large deletion in UL97 has a severe replication deficiency. J. Virol. 73 7 (1999) 5663-5670
67. Rivera J., Abrams C., Hernaez B., Alcazar A., Escribano J.M., Dixon L., and Alonso C. The MyD116 African swine fever virus homologue interacts with the catalytic subunit of protein phosphatase 1 and activates its phosphatase activity. J. Virol. 81 6 (2007) 2923-2929
68. Roby C., and Gibson W. Characterization of phosphoproteins and protein kinase activity of virions, noninfectious enveloped particles, and dense bodies of human cytomegalovirus. J. Virol. 59 3 (1986) 714-727
69. Rodems S.M., and Spector D.H. Extracellular signal-regulated kinase activity is sustained early during human cytomegalovirus infection. J. Virol. 72 11 (1998) 9173-9180
70. Sanchez V., McElroy A.K., Yen J., Tamrakar S., Clark C.L., Schwartz R.A., and Spector D.H. Cyclin-dependent kinase activity is required at early times for accurate processing and accumulation of the human cytomegalovirus UL122-123 and UL37 immediate-early transcripts and at later times for virus production. J. Virol. 78 20 (2004) 11219-11232
71. Scheuner D., Song B., McEwen E., Liu C., Laybutt R., Gillespie P., Saunders T., Bonner-Weir S., and Kaufman R.J. Translational control is required for the unfolded protein response and in vivo glucose homeostasis. Mol. Cell 7 6 (2001) 1165-1176
72. Shenolikar S. Protein serine/threonine phosphatases-new avenues for cell regulation. Annu. Rev. Cell. Biol. 10 (1994) 55-86
73. Spengler M.L., Kurapatwinski K., Black A.R., and Azizkhan-Clifford J. SUMO-1 modification of human cytomegalovirus IE1/IE72. J. Virol. 76 6 (2002) 2990-2996
74. Srivastava S.P., Kumar K.U., and Kaufman R.J. Phosphorylation of eukaryotic translation initiation factor 2 mediates apoptosis in response to activation of the double-stranded RNA-dependent protein kinase. J. Biol. Chem. 273 4 (1998) 2416-2423
75. Stamm S. Regulation of alternative splicing by reversible protein phosphorylation. J. Biol. Chem. 283 3 (2008) 1223-1227
76. Swingle M., Ni L., and Honkanen R.E. Small-molecule inhibitors of Ser/Thr protein phosphatases. In: Moorhead G. (Ed). Protein Phosphatase Protocols (2007), Humana Press, Totowa, NJ 23-38
77. Takizawa C.G., and Morgan D.O. Control of mitosis by changes in the subcellular location of cyclin-B1-Cdk1 and Cdc25C. Curr. Opin. Cell. Biol. 12 6 (2000) 658-665
78. Tan S.L., Tareen S.U., Melville M.W., Blakely C.M., and Katze M.G. The direct binding of the catalytic subunit of protein phosphatase 1 to the PKR protein kinase is necessary but not sufficient for inactivation and disruption of enzyme dimer formation. J. Biol. Chem. 277 39 (2002) 36109-36117
79. Tawara I., Nishikawa M., Morita K., Kobayashi K., Toyoda H., Omay S.B., Shima H., Nagao M., Kuno T., Tanaka C., et al. Down-regulation by retinoic acid of the catalytic subunit of protein phosphatase type 2A during granulocytic differentiation of HL-60 cells. FEBS Lett. 321 2-3 (1993) 224-228
80. Tolstykh T., Lee J., Vafai S., and Stock J.B. Carboxyl methylation regulates phosphoprotein phosphatase 2A by controlling the association of regulatory B subunits. EMBO J. 19 21 (2000) 5682-5691
81. Turowski P., Fernandez A., Favre B., Lamb N.J., and Hemmings B.A. Differential methylation and altered conformation of cytoplasmic and nuclear forms of protein phosphatase 2A during cell cycle progression. J. Cell. Biol. 129 2 (1995) 397-410
82. Varnum S.M., Streblow D.N., Monroe M.E., Smith P., Auberry K.J., Pasa-Tolic L., Wang D., Camp II D.G., Rodland K., Wiley S., Britt W., Shenk T., Smith R.D., and Nelson J.A. Identification of proteins in human cytomegalovirus (HCMV) particles: the HCMV proteome. J. Virol. 78 20 (2004) 10960-10966
83. Wilson N.J., Moss S.T., Csar X.F., Ward A.C., and Hamilton J.A. Protein phosphatase 2A is expressed in response to colony-stimulating factor 1 in macrophages and is required for cell cycle progression independently of extracellular signal-regulated protein kinase activity. Biochem. J. 339 Pt 3 (1999) 517-524
84. Yang Y.L., Reis L.F., Pavlovic J., Aguzzi A., Schafer R., Kumar A., Williams B.R., Aguet M., and Weissmann C. Deficient signaling in mice devoid of double-stranded RNA-dependent protein kinase. EMBO J. 14 24 (1995) 6095-6106
85. Zhang P., McGrath B., Li S., Frank A., Zambito F., Reinert J., Gannon M., Ma K., McNaughton K., and Cavener D.R. The PERK eukaryotic initiation factor 2 alpha kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas. Mol. Cell. Biol. 22 11 (2002) 3864-3874
86. Zhang P., McGrath B.C., Reinert J., Olsen D.S., Lei L., Gill S., Wek S.A., Vattem K.M., Wek R.C., Kimball S.R., Jefferson L.S., and Cavener D.R. The GCN2 eIF2alpha kinase is required for adaptation to amino acid deprivation in mice. Mol. Cell. Biol. 22 19 (2002) 6681-6688
87. Zsak L., Lu Z., Kutish G.F., Neilan J.G., and Rock D.L. An African swine fever virus virulence-associated gene NL-S with similarity to the herpes simplex virus ICP34.5 gene. J. Virol. 70 12 (1996) 8865-8871