Suppression of RIP3-dependent necroptosis by human cytomegalovirus

Journal of Biological Chemistry

Volumn 290, Issue 18, 2015, Pages 11635-11648

  Omoto, Shinya ^a,b   Guo, Hongyan ^a   Talekar, Ganesh R ^a,c   Roback, Linda ^a   Kaiser, William J ^a   Mocarski, Edward S ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b SHIONOGI AND CO LTD   (Japan)

^c NATIONAL CENTER FOR IMMUNIZATION AND RESPIRATORY DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOCHEMISTRY; BIOLOGY;

HUMAN CYTOMEGALOVIRUS; INFECTED CELLS; MEMBRANE LEAKAGES;

CHEMICAL ACTIVATION;

IMMEDIATE EARLY 1 PROTEIN; IMMEDIATE EARLY PROTEIN; MIXED LINEAGE KINASE; PROTEIN KINASE; RECEPTOR INTERACTING PROTEIN KINASE 3; TUMOR NECROSIS FACTOR RECEPTOR 1; UNCLASSIFIED DRUG; RECEPTOR INTERACTING PROTEIN SERINE THREONINE KINASE; RIPK3 PROTEIN, HUMAN;

APOPTOSIS; ARTICLE; BINDING COMPETITION; BINDING SITE; CELL CULTURE; CELL STRUCTURE; CELL VIABILITY; CONTROLLED STUDY; CYTOMEGALOVIRUS INFECTION; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; FIBROBLAST; GENE PRODUCT; HOST RESISTANCE; HUMAN; HUMAN CELL; HUMAN CYTOMEGALOVIRUS; INTRACELLULAR SIGNALING; NECROPTOSIS; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN LOCALIZATION; VIRUS GENE; VIRUS INHIBITION; ANIMAL; CYTOLOGY; CYTOMEGALOVIRUS; GENETIC TRANSDUCTION; GENETICS; METABOLISM; MOLECULAR EVOLUTION; MOUSE; MUROMEGALOVIRUS; NECROSIS; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; VIROLOGY;

HUMAN HERPESVIRUS 5; MURINAE; MUS;

ANIMALS; CYTOMEGALOVIRUS; EVOLUTION, MOLECULAR; FIBROBLASTS; HUMANS; IMMEDIATE-EARLY PROTEINS; MICE; MUROMEGALOVIRUS; NECROSIS; PHOSPHORYLATION; PROTEIN TRANSPORT; RECEPTOR-INTERACTING PROTEIN SERINE-THREONINE KINASES; RECEPTORS, TUMOR NECROSIS FACTOR, TYPE I; SIGNAL TRANSDUCTION; TRANSDUCTION, GENETIC;

EID: 84929500834     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.646042     Document Type: Article

References (100)

1. Lamkanfi, M., and Dixit, V. M. (2010) Manipulation of host cell death pathways during microbial infections. Cell Host Microbe 8, 44-54
2. Mocarski, E. S., Upton, J. W., and Kaiser, W. J. (2012) Viral infection and the evolution of caspase 8-regulated apoptotic and necrotic death pathways. Nat. Rev. Immunol. 12, 79-88
3. Sridharan, H., and Upton, J. W. (2014) Programmed necrosis in microbial pathogenesis. Trends Microbiol. 22, 199-207
4. Moquin, D., and Chan, F. K. (2010) The molecular regulation of programmed necrotic cell injury. Trends Biochem. Sci. 35, 434-441
5. Hedrick, S.M., Ch'en, I. L., andAlves, B.N. (2010) Intertwined pathways of programmed cell death in immunity. Immunol. Rev. 236, 41-53
6. Kaiser, W. J., Upton, J. W., and Mocarski, E. S. (2013) Viral modulation of programmed necrosis. Curr. Opin. Virol. 3, 296-306
7. Upton, J. W., and Chan, F. K. (2014) Staying alive: cell death in antiviral immunity. Mol. Cell 54, 273-280
8. Kaiser, W. J., Upton, J. W., Long, A. B., Livingston-Rosanoff, D., Daley-Bauer, L. P., Hakem, R., Caspary, T., and Mocarski, E. S. (2011) RIP3 mediates the embryonic lethality of caspase-8-deficient mice. Nature 471, 368-372
9. Vercammen, D., Beyaert, R., Denecker, G., Goossens, V., Van Loo, G., Declercq, W., Grooten, J., Fiers, W., and Vandenabeele, P. (1998) Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor. J. Exp. Med. 187, 1477-1485
10. Kawahara, A., Ohsawa, Y., Matsumura, H., Uchiyama, Y., and Nagata, S. (1998) Caspase-independent cell killing by Fas-associated protein with death domain. J. Cell Biol. 143, 1353-1360
11. Cho, Y. S., Challa, S., Moquin, D., Genga, R., Ray, T. D., Guildford, M., and Chan, F. K. (2009) Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell 137, 1112-1123
12. Upton, J. W., Kaiser, W.J., and Mocarski, E. S. (2010) Virus inhibition of RIP3-dependent necrosis. Cell Host Microbe 7, 302-313
13. Upton, J. W., Kaiser, W. J., and Mocarski, E. S. (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
14. Feoktistova, M., Geserick, P., Panayotova-Dimitrova, D., and Leverkus, M. (2012) Pick your poison: The ripoptosome, a cell death platform regulating apoptosis and necroptosis. Cell Cycle 11, 460-467
15. Kaiser, W. J., Daley-Bauer, L. P., Thapa, R. J., Mandal, P., Berger, S. B., Huang, C, Sundararajan, A., Guo, H., Roback, L., Speck, S. H., Bertin, J., Gough, P. J., Balachandran, S., and Mocarski, E. S. (2014) RIP1 suppresses innate immune necrotic as well as apoptotic cell death during mammalian parturition. Proc. Natl. Acad. Sci. U.S.A. 111, 7753-7758
16. Thapa, R. J., Nogusa, S., Chen, P., Maki, J. L., Lerro, A., Andrake, M., Rall, G. F., Degterev, A., and Balachandran, S. (2013) Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases. Proc. Natl. Acad. Sci. U.S.A. 110, 3109-3118
17. Kaiser, W. J., Sridharan, H., Huang, C, Mandal, P., Upton, J. W., Gough, P. J., Sehon, C. A., Marquis, R. W., Bertin, J., and Mocarski, E. S. (2013) Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL.J. Biol. Chem. 288, 31268-31279
18. Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Valitutti, S., Bodmer, J. L., Schneider, P., Seed, B., and Tschopp, J. (2000) Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat. Immunol. 1, 489-495
19. Micheau, O., Thome, M., Schneider, P., Holler, N., Tschopp, J., Nicholson, D. W., Briand, C, and Grütter, M. G. (2002) The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex. J. Biol. Chem. 277, 45162-45171
20. Micheau, O., and Tschopp, J. (2003) Induction of TNF receptor I-medi-ated apoptosis via two sequential signaling complexes. Cell 114, 181-190
21. Degterev, A., Huang, Z., Boyce, M., Li, Y., Jagtap, P., Mizushima, N, Cuny, G. D., Mitchison, T. J., Moskowitz, M. A., and Yuan, J. (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem. Biol. 1, 112-119
22. He, S., Wang, L., Miao, L., Wang, T., Du, F., Zhao, L., and Wang, X. (2009) Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-a. Cell 137, 1100-1111
23. Zhang, D. W., Shao, J., Lin, J., Zhang, N, Lu, B. J., Lin, S. C, Dong, M. Q., and Han, J. (2009) RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science 325, 332-336
24. Chan, F. K., Shisler, J., Bixby, J. G., Felices, M., Zheng, L., Appel, M., Orenstein, J., Moss, B., and Lenardo, M. J. (2003) A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. J. Biol. Chem. 278, 51613-51621
25. Berger, A. K., and Danthi, P. (2013) Reovirus activates a caspase-independent cell death pathway. mBio 4, e00178-00113
26. Rebsamen, M., Heinz, L. X., Meylan, E., Michallet, M. C, Schroder, K., Hofmann, K., Vazquez, J., Benedict, C A., and Tschopp, J. (2009) DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-KB. EMBO Rep. 10, 916-922
27. Upton, J. W., Kaiser, W. J., and Mocarski, E. S. (2008) Cytomegalovirus M45 cell death suppression requires receptor-interacting protein (RIP) homotypic interaction motif (RHIM)-dependent interaction with RIP1. J. Biol. Chem. 283, 16966-16970
28. He, S., Liang, Y., Shao, F., and Wang, X. (2011) Toll-like receptors activate programmed necrosis in macrophages through a receptor-interacting kinase-3-mediated pathway. Proc. Natl. Acad. Sci. U.S.A. 108, 20054-20059
29. Li, J., McQuade, T., Siemer, A. B., Napetschnig, J., Moriwaki, K., Hsiao, Y. S., Damko, E., Moquin, D., Walz, T., McDermott, A., Chan, F. K., and Wu, H. (2012) The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell 150, 339-350
30. Mandal, P., Berger, S. B., Pillay, S., Moriwaki, K., Huang, C, Guo, H., Lich, J. D., Finger, J., Kasparcova, V., Votta, B., Ouellette, M., King, B. W., Wisnoski, D., Lakdawala, A. S., DeMartino, M. P., Casillas, L. N, Haile, P. A., Sehon, C A., Marquis, R. W., Upton, J., Daley-Bauer, L. P., Roback, L., Ramia, N, Dovey, C. M., Carette, J. E., Chan, F. K., Bertin, J., Gough, P. J., Mocarski, E. S., and Kaiser, W. J. (2014) RIP3 induces apoptosis independent of pro-necrotic kinase activity. Mol. Cell 56, 481-495
31. Sun, L., Wang, H., Wang, Z., He, S., Chen, S., Liao, D., Wang, L., Yan, J., Liu, W., Lei, X., and Wang, X. (2012) Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148, 213-227
32. Zhao, J., Jitkaew, S., Cai, Z., Choksi, S., Li, Q., Luo, J., and Liu, Z. G. (2012) Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis. Proc. Natl. Acad. Sci. U.S.A. 109, 5322-5327
33. Vandenabeele, P., Declercq, W., Van Herreweghe, F., and Vanden Ber-ghe, T. (2010) The role of the kinases RIP1 and RIP3 in TNF-induced necrosis. Sci. Signal. 3, re4
34. Murphy, J. M., Czabotar, P. E., Hildebrand, J. M., Lucet, I. S., Zhang, J. G., Alvarez-Diaz, S., Lewis, R., Lalaoui, N, Metcalf, D., Webb, A. I., Young, S. N, Varghese, L. N, Tannahill, G. M., Hatchell, E. C, Majewski, I. J., Okamoto, T., Dobson, R. C, Hilton, D. J., Babon, J. J., Nicola, N. A., Strasser, A., Silke, J., and Alexander, W. S. (2013) The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 39, 443-453
35. Cai, Z., Jitkaew, S., Zhao, J., Chiang, H. C, Choksi, S., Liu, J., Ward, Y., Wu, L. G., and Liu, Z. G. (2014) Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis. Nat. Cell Biol. 16, 55-65
36. Chen, X., Li, W., Ren, J., Huang, D., He, W. T., Song, Y., Yang, C, Li, W., Zheng, X., Chen, P., and Han, J. (2014) Translocation of mixed lineage kinase domain-like protein to plasma membrane leads to necrotic cell death. Cell Res. 24, 105-121
37. Antonopoulos, C, El Sanadi, C, Kaiser, W. J., Mocarski, E. S., and Dub-yak, G. R. (2013) Pro-apoptotic chemotherapeutic drugs induce non-canonical processing and release of IL-1β via caspase-8 in dendritic cells. J. Immunol. 191, 4789-4803
38. Weng, D., Marty-Roix, R., Ganesan, S., Proulx, M. K., Vladimer, G. I., Kaiser, W. J., Mocarski, E. S., Pouliot, K., Chan, F. K., Kelliher, M. A., Harris, P. A., Bertin, J., Gough, P. J., Shayakhmetov, D. M., Goguen, J. D., Fitzgerald, K. A., Silverman, N., and Lien, E. (2014) Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death. Proc. Natl. Acad. Sci. U.S.A. 111, 7391-7396
39. Philip, N. H., Dillon, C P., Snyder, A. G., Fitzgerald, P., Wynosky-Dolfi, M. A., Zwack, E. E., Hu, B., Fitzgerald, L., Mauldin, E. A., Copenhaver, A. M., Shin, S., Wei, L., Parker, M., Zhang, J., Oberst, A., Green, D. R., and Brodsky, I.E. (2014) Caspase-8 mediates caspase-1 processing and innate immune defense in response to bacterial blockade of NF-KB and MAPK signaling. Proc. Natl. Acad. Sci. U.S.A. 111, 7385-7390
40. Li, M., and Beg, A. A. (2000) Induction of necrotic-like cell death by tumor necrosis factor alpha and caspase inhibitors: novel mechanism for killing virus-infected cells. J. Virol. 74, 7470-7477
41. Guo, H., Omoto, S., Harris, P. A., Finger, J. N, Bertin, J., Gough, P. J., Kaiser, W. J., and Mocarski, E. S. (2015) Herpes simplex virus suppression of necroptosis in human cells. Cell Host Microbe 17, 243-251
42. Xie, T., Peng, W., Yan, C, Wu, J., Gong, X., and Shi, Y. (2013) Structural insights into RIP3-mediated necroptotic signaling. Cell Rep. 5, 70-78
43. Mack, C., Sickmann, A., Lembo, D., and Brune, W. (2008) Inhibition of proinflammatory and innate immune signaling pathways by a cytomegalovirus RIP1-interacting protein. Proc. Natl. Acad. Sci. U.S.A. 105, 3094-3099
44. Brune, W., Menard, C., Heesemann, J., and Koszinowski, U. H. (2001) A ribonucleotide reductase homolog of cytomegalovirus and endothelial cell tropism. Science 291, 303-305
45. Brune, W. (2011) Inhibition of programmed cell death by cytomegaloviruses. Virus Res. 157, 144-150
46. Lembo, D., Donalisio, M., Hofer, A., Cornaglia, M., Brune, W., Koszinowski, U., Thelander, L., and Landolfo, S. (2004) The ribonucleotide reductase R1 homolog of murine cytomegalovirus is not a functional enzyme subunit but is required for pathogenesis. J. Virol. 78, 4278-4288
47. Mocarski, E. S., Kaiser, W. J., Livingston-Rosanoff, D., Upton, J. W., and Daley-Bauer, L. P. (2014) True grit: programmed necrosis in antiviral host defense, inflammation, and immunogenicity. J. Immunol. 192, 2019-2026
48. Fliss, P. M., Jowers, T. P., Brinkmann, M. M., Holstermann, B., Mack, C., Dickinson, P., Hohenberg, H., Ghazal, P., and Brune, W. (2012) Viral mediated redirection of NEMO/IKK7 to autophagosomes curtails the inflammatory cascade. PLoS Pathog. 8, e1002517
49. Krause, E., de Graaf, M., Fliss, P. M., Dolken, L., and Brune, W. (2014) Murine cytomegalovirus virion-associated protein M45 mediates rapid NF-KB activation after infection. J. Virol. 88, 9963-9975
50. Dufour, F., Sasseville, A. M., Chabaud, S., Massie, B., Siegel, R. M., and Langelier, Y. (2011) The ribonucleotide reductase R1 subunits of herpes simplex virus types 1 and 2 protect cells against TNFalpha-and FasL-induced apoptosis by interacting with caspase-8. Apoptosis 16, 256-271
51. Wang, X., Li, Y., Liu, S., Yu, X., Li, L., Shi, C., He, W., Li, J., Xu, L., Hu, Z., Yu, L., Yang, Z., Chen, Q., Ge, L., Zhang, Z., Zhou, B., Jiang, X., Chen, S., and He, S. (2014) Direct activation of RIP3/MLKL-dependent necrosis by herpes simplex virus 1 (HSV-1) protein ICP6 triggers host antiviral defense. Proc. Natl. Acad. Sci. U.S.A. 111, 15438-15443
52. Huang, Z., Wu, S.-Q., Liang, Y., Zhou, X., Chen, W., Li, L., Wu, J., Zhuang, Q., Chen, C, Li, J., Zhong, C, Xia, W., Zhou, R., Zheng, C, and Han, J. (2015) Targeting HSV-1 protein ICP6 by RIP1 and RIP3 initiates necroptosis to restrict HSV-1 propagation in mice. Cell Host Microbe 17, 229-242
53. Skaletskaya, A., Bartle, L. M., Chittenden, T., McCormick, A. L., Mocarski, E. S., and Goldmacher, V. S. (2001) A cytomegalovirus-encoded inhibitor of apoptosis that suppresses caspase-8 activation. Proc. Natl. Acad. Sci. U.S.A. 98, 7829-7834
54. McCormick, A. L., Skaletskaya, A., Barry, P. A., Mocarski, E. S., and Goldmacher, V. S. (2003) Differential function and expression of the viral inhibitor of caspase 8-induced apoptosis (vICA) and the viral mitochondria-localized inhibitor of apoptosis (vMIA) cell death suppressors conserved in primate and rodent cytomegaloviruses. Virology 316, 221-233
55. Menard, C, Wagner, M., Ruzsics, Z., Holak, K., Brune, W., Campbell, A. E., and Koszinowski, U. H. (2003) Role of murine cytomegalovirus US22 gene family members in replication in macrophages. J. Virol. 77, 5557-5570
56. Cicin-Sain, L., Ruzsics, Z., Podlech, J., Bubic, I., Menard, C, Jonjic, S., Reddehase, M. J., and Koszinowski, U. H. (2008) Dominant-negative FADD rescues the in vivo fitness of a cytomegalovirus lacking an antiapo-ptotic viral gene. J. Virol. 82, 2056-2064
57. McCormick, A. L., Roback, L., Livingston-Rosanoff, D., and St Clair, C. (2010) The human cytomegalovirus UL36 gene controls caspase-dependent and-independent cell death programs activated by infection of monocytes differentiating to macrophages. J. Virol. 84, 5108-5123
58. McCormick, A. L., and Mocarski, E. S. (2013) Cell death pathways controlled by cytomegaloviruses. in Cytomegaloviruses: From Molecular Pathogenesis to Intervention (Reddehase, M. J., ed) pp. 263-276, Caister Scientific Press, Norfolk, UK
59. Daley-Bauer, L. P., and Mocarski, E. S. (2013) Myeloid cell recruitment and function in cytomegalovirus immunity and pathogenesis. in Cytomegaloviruses: From Molecular Pathogenesis to Intervention (Reddehase, M. J., ed) pp. 363-373, Caister Scientific Press, Norfolk, UK
60. Goldmacher, V. S., Bartle, L. M., Skaletskaya, A., Dionne, C.A., Kedersha, N. L., Vater, C. A., Han, J. W., Lutz, R. J., Watanabe, S., Cahir McFarland, E. D., Kieff, E. D., Mocarski, E. S., and Chittenden, T. (1999) A cytomegalovirus-encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2. Proc. Natl. Acad. Sci. U.S.A. 96, 12536-12541
61. Karbowski, M., Norris, K. L., Cleland, M. M., Jeong, S. Y., and Youle, R. J. (2006) Role of Bax and Bak in mitochondrial morphogenesis. Nature 443, 658-662
62. Cam, M., Handke, W., Picard-Maureau, M., and Brune, W. (2010) Cytomegaloviruses inhibit Bak-and Bax-mediated apoptosis with two separate viral proteins. Cell Death Differ. 17, 655-665
63. Manzur, M., Fleming, P., Huang, D. C, Degli-Esposti, M. A., and Ando-niou, C. E. (2009) Virally mediated inhibition of Bax in leukocytes promotes dissemination of murine cytomegalovirus. Cell Death Differ. 16, 312-320
64. Crosby, L. N, McCormick, A. L., and Mocarski, E. S. (2013) Gene products of the embedded m41/m41.1 locus of murine cytomegalovirus differentially influence replication and pathogenesis. Virology 436, 274-283
65. Handke, W., Luig, C, Popovic, B., Krmpotic, A., Jonjic, S., and Brune, W. (2013) Viral inhibition of BAK promotes murine cytomegalovirus dissemination to salivary glands. J. Virol. 87, 3592-3596
66. Fleming, P., Kvansakul, M., Voigt, V., Kile, B. T., Kluck, R. M., Huang, D. C, Degli-Esposti, M. A., and Andoniou, C. E. (2013) MCMV-medi-ated inhibition of the pro-apoptotic Bak protein is required for optimal in vivo replication. PLoS Pathog. 9, e1003192
67. McCormick, A. L. (2008) Control of apoptosis by human cytomegalovirus. Curr. Top. Microbiol. Immunol. 325, 281-295
68. McCormick, A. L., Roback, L., Wynn, G., and Mocarski, E. S. (2013) Multiplicity-dependent activation of a serine protease-dependent cyto-megalovirus-associated programmed cell death pathway. Virology 435, 250-257
69. Zhu, H., Shen, Y., and Shenk, T. (1995) Human cytomegalovirus IE1 and IE2 proteins block apoptosis. J. Virol. 69, 7960-7970
70. Greaves, R. F., and Mocarski, E. S. (1998) Defective growth correlates with reduced accumulation of a viral DNA replication protein after low multiplicity infection by a human cytomegalovirus ie1 mutant. J. Virol. 72, 366-379
71. Green, D. R., and Victor, B. (2012) The pantheon of the fallen: why are there so many forms of cell death? Trends Cell Biol. 22, 555-556
72. Moriwaki, K., and Chan, F. K. (2013) RIP3: a molecular switch for necrosis and inflammation. Genes Dev. 27, 1640-1649
73. Le, V. T., Trilling, M., and Hengel, H. (2011) The cytomegaloviral protein pUL138 acts as potentiator of tumor necrosis factor (TNF) receptor 1 surface density to enhance ULb'-encoded modulation of TNF-a signaling. J. Virol. 85, 13260-13270
74. Montag, C, Wagner, J. A., Gruska, I., Vetter, B., Wiebusch, L., and Hage-meier, C. (2011) The latency-associated UL138 gene product of human cytomegalovirus sensitizes cells to tumor necrosis factor a (TNF-a) signaling by upregulating TNF-a receptor 1 cell surface expression. J. Virol. 85, 11409-11421
75. Sarbassov, D. D., Guertin, D. A., Ali, S. M., and Sabatini, D. M. (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307, 1098-1101
76. Naldini, L., Blomer, U, Gage, F. H, Trono, D., and Verma, I. M. (1996) Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc. Natl. Acad. Sci. U.S.A. 93, 11382-11388
77. Omoto, S., and Mocarski, E. S. (2013) Cytomegalovirus UL91 is essential for transcription of viral true late (72) genes. J. Virol. 87, 8651-8664
78. Marchini, A., Liu, H., and Zhu, H. (2001) Human cytomegalovirus with IE-2 (UL122) deleted fails to express early lytic genes. J. Virol. 75, 1870-1878
79. Kaiser, W. J., and Offermann, M. K. (2005) Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif. J. Immunol. 174, 4942-4952
80. Varfolomeev, E., Blankenship, J. W., Wayson, S. M., Fedorova, A. V., Kayagaki, N, Garg, P., Zobel, K., Dynek, J. N, Elliott, L. O., Wallweber, H. J., Flygare, J. A., Fairbrother, W. J., Deshayes, K., Dixit, V. M., and Vucic, D. (2007) IAP antagonists induce autoubiquitination of c-IAPs, NF-KB activation, and TNFa-dependent apoptosis. Cell 131, 669-681
81. Müller-Sienerth, N, Dietz, L., Holtz, P., Kapp, M., Grigoleit, G. U., Schmuck, C., Wajant, H., and Siegmund, D. (2011) SMAC mimetic BV6 induces cell death in monocytes and maturation of monocyte-derived dendritic cells. PLoS One 6, e21556
82. Lin, Y., Devin, A., Rodriguez, Y., and Liu, Z. G. (1999) Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev. 13, 2514-2526
83. Feng, S., Yang, Y., Mei, Y., Ma, L., Zhu, D. E., Hoti, N, Castanares, M., and Wu, M. (2007) Cleavage of RIP3 inactivates its caspase-independent apoptosis pathway by removal of kinase domain. Cell. Signal. 19, 2056-2067
84. Oberst, A., Dillon, C. P., Weinlich, R., McCormick, L. L., Fitzgerald, P., Pop, C, Hakem, R., Salvesen, G. S., and Green, D. R. (2011) Catalytic activity of the caspase-8-FLIP(L) complex inhibits RIPK3-dependent necrosis. Nature 471, 363-367
85. Sun, X., Yin, J., Starovasnik, M. A., Fairbrother, W. J., and Dixit, V. M. (2002) Identification of a novel homotypic interaction motif required for the phosphorylation of receptor-interacting protein (RIP) byRIP3.J. Biol. Chem. 277, 9505-9511
86. Manning, W. C, Murphy, J. E., Jolly, D. J., Mento, S. J., and Ralston, R. O. (1998) Use of a recombinant murine cytomegalovirus expressing vesicular stomatitis virus G protein to pseudotype retroviral vectors. J. Virol. Methods 73, 31-39
87. Walker, D., and Hudson, J. (1987) Analysis of immediate-early and early proteins of murine cytomegalovirus in permissive and nonpermissive cells. Arch. Virol. 92, 103-119
88. Jurak, I., and Brune, W. (2006) Induction of apoptosis limits cytomegalovirus cross-species infection. EMBOJ. 25, 2634-2642
89. Kaarbø, M., Ager-Wick, E., Osenbroch, P. Ø., Kilander, A., Skinnes, R., Müller, F., and Eide, L. (2011) Human cytomegalovirus infection increases mitochondrial biogenesis. Mitochondrion 11, 935-945
90. Lafemina, R. L., and Hayward, G. S. (1988) Differences in cell-type-specific blocks to immediate early gene expression and DNA replication of human, simian and murine cytomegalovirus. J. Gen. Virol. 69, 355-374
91. Stinski, M. F., and Meier, J. L. (2007) Immediate-early CMV gene regulation and function. in Human Herpesviruses: Biology, Therapy and Im-munoprophylaxis, 2011/02/25 Ed. (Arvin, A. M., Campadelli-Fiume, G., Mocarski, E. S., Moore, P. S., Roizman, B., Whitley, R., and Yamanishi, K., eds) pp. 241-263, Cambridge Press, Cambridge, UK
92. Paulus, C, and Nevels, M. (2009) The human cytomegalovirus major immediate-early proteins as antagonists of intrinsic and innate antiviral host responses. Viruses 1, 760-779
93. Lembo, D., and Brune, W. (2009) Tinkering with a viral ribonucleotide reductase. Trends Biochem. Sci. 34, 25-32
94. Hahn, G., Khan, H, Baldanti, F., Koszinowski, U. H., Revello, M. G., and Gerna, G. (2002) The human cytomegalovirus ribonucleotide reductase homolog UL45 is dispensable for growth in endothelial cells, as determined by a BAC-cloned clinical isolate of human cytomegalovirus with preserved wild-type characteristics. J. Virol. 76, 9551-9555
95. Patrone, M., Percivalle, E., Secchi, M., Fiorina, L., Pedrali-Noy, G., Zoppe, M., Baldanti, F., Hahn, G., Koszinowski, U H, Milanesi, G., and Gallina, A. (2003) The human cytomegalovirus UL45 gene product is a late, viri-on-associated protein and influences virus growth at low multiplicities of infection. J. Gen. Virol. 84, 3359-3370
96. Baillie, J., Sahlender, D. A., and Sinclair, J. H. (2003) Human cytomegalovirus infection inhibits tumor necrosis factor a (TNF-a) signaling by targeting the 55-kilodalton TNF-a receptor. J. Virol. 77, 7007-7016
97. Smith, W., Tomasec, P., Aicheler, R., Loewendorf, A., Nemcovicova, I., Wang, E. C, Stanton, R. J., Macauley, M., Norris, P., Willen, L., Ruckova, E., Nomoto, A., Schneider, P., Hahn, G., Zajonc, D. M., Ware, C. F., Wilkinson, G. W., and Benedict, C A. (2013) Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses. Cell Host Microbe 13, 324-335
98. Seirafian, S., Prod'homme, V., Sugrue, D., Davies, J., Fielding, C, Tomasec, P., and Wilkinson, G. W. (2014) Human cytomegalovirus suppresses Fas expression and function. J. Gen. Virol. 95, 933-939
99. DeFilippis, V. R., Alvarado, D., Sali, T., Rothenburg, S., and Früh, K. (2010) Human cytomegalovirus induces the interferon response via the DNA sensor ZBP1.J. Virol. 84, 585-598
100. Kaiser, W. J., Upton, J. W., and Mocarski, E. S. (2008) Receptor-interacting protein homotypic interaction motif-dependent control of NF-KB activation via the DNA-dependent activator of IFN regulatory factors. J. Immunol. 181, 6427-6434