Apoptosis regulators from DNA viruses

Current Opinion in Immunology

Volumn 10, Issue 4, 1998, Pages 422-430

  Barry, Michele ^a   McFadden, Grant ^b  

^a UNIVERSITY OF ALBERTA   (Canada)

^b ROBARTS RESEARCH INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

FAS ANTIGEN; INTERFERON; OXIDE; PROTEIN BCL 2; PROTEIN KINASE; SCAVENGER; TUMOR NECROSIS FACTOR;

APOPTOSIS; CELL CYCLE; DNA VIRUS; ENDOPLASMIC RETICULUM; HUMAN; NONHUMAN; PROTEIN EXPRESSION; REVIEW; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION;

EID: 0032146728     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(98)80116-7     Document Type: Article

References (95)

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33. of special interest Izumi KM, Kieff ED. The Epstein-Barr virus oncogene product latent membrane protein 1 engages the tumor necrosis factor receptor-associated death domain protein to mediate B lymphocyte growth transformation and activate NF-κB. Proc Natl Acad Sci USA. 94:1997;12592-12597 This work shows that one transformation effector site (TES2) at the carboxyl terminus of LMP-1 binds TNF-receptor-associated death-domain protein (TRADD). The associated TRADD-LMP-1 complex was responsible for the activation of the transcription factor NF-κB associated with the constitutive signalling of LMP-1.
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47. of special interest Rao L, Modha D, White E. The E1B 19k protein associates with lamins in vivo and its proper localization is required for inhibition. Oncogene. 15:1997;1587-1597 This paper describes the in vivo and in vivo association of the adenovirus Bcl-2 homolog, E1B-19K, with lamins A and C. The authors show that E1B-19K's interaction with lamins is necessary for proper localization of the protein to membranes and is essential for apoptosis inhibition; furthermore, Bcl-2 does not interact with lamins, indicating that lamin association is a unique property of E1B-19K.
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52. of outstanding interest Chiou S-K, White E. p300 binding by E1A cosegregates with p53 induction but is dispensable for apoptosis. J Virol. 71:1997;3515-3525 Several groups demonstrated that the adenovirus early gene product E1A for the transcriptional coactivated p300/CBP is critical for p53 upregulation by this viral protein. This paper shows that mutants of E1A deficient for both p300/CBP binding and p53 accumulation can still nevertheless induce apoptosis in HeLa cells. This is consistent with E1A's suspected ability to facilitate distinct apoptosis pathways that are p53-dependent and p53-independent.
53. of outstanding interest Querido E, Teodoro JG, Branton PE. Accumulation of p53 induced by the adenovirus E1A protein requires regions involved in the stimulation of DNA synthesis. J Virol. 71:1997;3526-3533 This paper is similar to [52], at least in showing that the domain of E1A that binds the transcriptional coactivators p300/CBP is critical for p53 upregulation. In this paper, however, p300 binding to E1A correlated with induction of apoptosis in HeLa cells, while in MRC-5 cells this function could be subserved by the domain that binds the cell regulator pRB, suggesting that the two E1A domains could function in a redundant fashion, depending on the cell type. Importantly, E1A could still induce apoptosis in p53-null cells, reaffirming the importance of the p53-independent pathway.
54. Samuelson AV, Lowe SW. Selective induction of p53 and chemosensitivity in RB-deficient cells by E1A mutants unable to bind the RB-related proteins. Proc Natl Acad Sci USA. 94:1997;12094-12099.
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57. of special interest Rubenwolf S, Schütt H, Nevels M, Wolf H, Dobner T. Structural analysis of the adenovirus type 5 E1B 55-kilodalton-E4orf6 protein complex. J Virol. 71:1997;1115-1123 This paper, together with [58-60], is one of four reports showing that E4orf6 forms a p53-inhibitory complex with E1B-55K. The authors utilize mutants of the two viral proteins to map the interaction domains and show that p53 is not required to form the complex. The amino-terminus of E4orf6 is critical, while two central regions of E1B-55k provide overlapping, but not identical, binding domains for E4orf6 and p53.
58. of special interest Querido E, Marcellus RC, Lai A, Charbonneau R, Teodoro JG, Ketner G, Branton PE. Regulation of p53 levels by the E1B 55-kilodalton protein and E4orf6 in adenovirus-infected cells. J Virol. 71:1997;3788-3798 These authors confirm the interaction between the adenovirus proteins E4orf6 and E1B-55K, and show the 243R protein product of the adenovirus early gene product E1A, but not 289R, induces the accumulation of p53 protein, which is degraded when both E1B-55K and E4orf6 are expressed. They also demonstrate that the failure to accumulate p53 in the presence of both viral proteins cannot be explained by the generalized shutoff of host protein synthesis.
59. of special interest Nevels M, Rubenwolf S, Spruss T, Wolf H, Dobner T. The adenovirus E4orf6 protein can promote E1A/E1B-induced focus formation by interfering with p53 tumor suppressor function. Proc Natl Acad Sci USA. 94:1997;1206-1211 This paper uses transformation assays, rather than apoptosis, to demonstrate the role of E4orf6 in co-operating with another adenovirus protein, E1B-55K, to block the ability of the early virus gene product, E1A, to interfere with p53 functions. The authors also confirm that in the presence of both E1B-55K and E4orf6, p53 is efficiently degraded.
60. of special interest Steegenga WT, Riteco N, Jochemsen AG, Fallaux FJ, Bos JL. The large E1B protein together with the E4orf6 protein target p53 for active degradation in adenovirus infected cells. Oncogene. 16:1998;349-357 This is the fourth paper, together with [57-59], to demonstrate that the adenovirus proteins E1B-55K and E4orf6 co-operate to ensure that p53 levels do not rise in response to the early viral gene product E1A. The degradation of p53 did not require E1A, and was not affected by stabilizing mutations in p53.
61. Heise C, Sampsonjohannes A, Williams A, McCormick F, Vonhoff DD, Kirn DH. Onyx-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficiency that can be augmented by standard chemotherapeutic agents. Nat Med. 3:1997;639-645.
62. of special interest Chirillo P, Pagano S, Natoli G, Puri PL, Burgio VL, Balano C, Levrero M. The hepatitis B virus X gene induces p53-mediated programmed cell death. Proc Natl Acad Sci USA. 94:1997;8162-8167 Several groups have now shown that the pX protein of hepatitis B virus can regulate p53-dependent apoptosis. In this work, the authors show that pX induces both DNA synthesis and apoptosis in response to serum starvation, reduces clonogenic survival when cells express p53 and can be blocked by dominant-negative mutations in c-myc. Interestingly, in p53-null cells, pX induces cell growth rather than apoptosis.
63. of special interest Su F, Schneider RJ. Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor necrosis factor a. Proc Natl Acad Sci USA. 94:1997;8744-8749 This work demonstrates that the hepatitis B protein pX sensitizes cells to apoptosis induced by TNF. Mitogenic stimulation of Chang liver cells could suppress the pX sensitization, suggesting that neoplastic hepatocytes might escape pX-induced killing by producing mitogenic growth factors and thus contribute to hepatocarcinoma development.
64. of special interest Elmore LW, Hancock AR, Chang S-F, Wang XW, Chang S, Callahan CP, Geller DA, Will H, Harris C. Hepatitis B virus X protein and p53 tumor suppressor interactions in the modulation of apoptosis. Proc Natl Acad Sci USA. 94:1997;14707-14712 These workers demonstrate direct binding between p53 and pX and map the distal carboxyl terminus of hepatitis B protein pX as critical for the interaction. The pX-p53 complex was found to be sequestered in the cytoplasm and thus presumably rendered the complex unable to induce p53-responsive gene (see also [67]). Interestingly, the pX transactivation domain comapped with its p53-binding domain (residues 111-154), but subtype analysis revealed that these two activities could be segregated from each other (as in [65]).
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67. Takada S, Kaneniwa N, Tsuchida N, Koike C. Cytoplasmic retention of the p53 tumor suppressor gene product is observed in the hepatitis B virus X gene-transfected cells. Oncogene. 15:1997;1895-1901.
68. Barnabas S, Hai T, Andrisani OM. The hepatitis B virus X protein enhances the DNA binding potential and transcription efficacy of bZip transcription factors. J Biol Chem. 272:1997;20684-20690.
69. Jones DL, Thompson DA, Münger K. Destabilization of the RB tumor suppressor protein and stabilization of p53 contribute to HPV type 16 E7-induced apoptosis. Virology. 239:1997;97-107.
70. of special interest Magal SS, Jackman A, Pei XF, Schlegel R, Sherman L. Induction of apoptosis in human keratinocytes containing mutated p53 alleles and its inhibition by both the E6 and E7 oncoproteins. Int J Cancer. 75:1998;96-104 The E6 and E7 oncoproteins of human papillomavirus were known to prevent p53-mediated cell cycle arrest following DNA damage, but their roles in apoptosis induction are complex. This work shows that in HaCaT cells, a keratinocyte derived cell line with mutated p53, UV-induced S phase and apoptosis could be blocked by either E6 or E7 expressed from recombinant retrovirus vectors.
71. Jung Y-K, Yuan J. Suppression of Interleukin-1b converting enzyme (ICE)-induced apoptosis by SV40 large T antigen. Oncogene. 14:1997;1207-1214.
72. Conzen SD, Snay CA, Cole CN. Identification of a novel antiapoptotic functional domain in simian virus 40 large T antigen. J Virol. 71:1997;4536-4543.
73. of special interest Dahl J, Jurczak A, Cheng LA, Baker DC, Benjamin TL. Evidence of a role for phosphatidylinositol 3-kinase activation in the blocking of apoptosis by polyomavirus middle T antigen. J Virol. 72:1998;3221-3226 The principal transforming oncoprotein of polyoma virus, middle-T antigen, doesn't bind or affect p53 but interacts with a variety of other cellular proteins, including PI-3 kinase. These authors show that the complex of PI-3 kinase and middle-T antigen activates Akt, a kinase that directly phosphorylates key apoptosis regulators such as the bcl-2-relative Bad, and protects polyoma transformed cells from apoptosis.
74. Frattini MG, Hurst SD, Lim HB, Swaminathan S, Laimins LA. Abrogation of a mitotic checkpoint by E2 proteins from oncogenic human papillomavirus correlates with increased turnover of the p53 tumor suppressor protein. EMBO J. 16:1997;318-331.
75. Sanchez-Perez A-M, Soriano S, Clarke AR, Gaston K. Disruption of the human papillomavirus type 16 E2 gene protects cervical carcinoma cells from E2F-induced apoptosis. J Gen Virol. 78:1997;3009-3018.
76. + HeLa cell line repressed E6 and E7 transcription, induced p53-regulated gene expression and triggered apoptosis. Although the induction required p53, the E2-activated apoptosis could be distinguished from E2-mediated cdll cycle arrest by mutational analysis.
77. Liu JL, Lee LF, Ye Y, Qian Z, Kung H-J. Nucleolar and nuclear localization properties of a herpesvirus bZip oncoprotein, MEQ. J Virol. 71:1997;3188-3196.
78. of special interest Liu J-L, Ye Y, Lee LF, Kung H-J. Transforming potential of the herpesvirus oncoprotein MEQ: Morphological transformation, serum-independent growth, and inhibition of apoptosis. J Virol. 72:1998;388-395 MEQ is a transforming oncoprotein of Maerk's disease virus and is a member of the bZIP leucine-zipper transcription factor family that transactivates viral and cellular genes. This paper shows that Rat-2 cells can be transformed with MEQ and become resistant to apoptosis inducers such as TNF, ceramide, UV and serum deprivation. The induction of bcl-2 and repression of bax in these cells is believed to be due to MEQ transactivation, but this remains to be proven. The only other case of herpesvirus transcription factors that block apoptosis are the IE1/2 proteins of cytomegalovirus, although several other herpesvirus transactivator proteins do bind p53.
79. Diaz-Guerra M, Rivas C, Esteban M. Inducible expression of the 2-5A synthetase/RNase L system results in inhibition of vaccinia virus replication. Virology. 227:1997;220-228.
80. of special interest Diaz-Guerra M, Rivas C, Esteban M. Activation of the IFN-inducible enzyme RNase L causes apoptosis of animal cells. Virology. 236:1997;354-363 Although it is known that an activated mediator of apoptosis, PKR, alone can induce apoptosis, the role of the other major interferon-inducible protein that is activated by double-stranded RNA, namely RNAse L, has been unclear. This paper and its companion (refrence [79]) are the first studies to demonstrate that activated RNAse L in the absence of PKR will also induce apoptosis by itself. This apoptosis is potentiated by coexpression of 2-5A synthetase and can be inhbited by bcl-2.
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82. Der SD, Yang Y-L, Weissman C, Williams BRG. A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis. Proc Natl Acad Sci USA. 94:1997;3279-3283.
83. Lee SB, Rodriguez D, Rodriguez JR, Esteban M. The apoptosis pathway triggered by the interferon-induced protein kinase PKR requires the third basic domain, initiates upstream of Bcl-2, and involves ICE-like proteases. Virology. 231:1997;81-88.
84. of special interest Kibler KV, Shors T, Perkins KB, Zeman CC, Banaszak MP, Biesterfeldt J, Langland JO, Jacobs BL. Double-stranded RNA is a trigger for apoptosis in vaccinia virus-infected cells. J Virol. 71:1997;1992-2003 This paper and a closely related companion (reference [86]) show clearly that in vaccina virus deleted for the dsRNA-binding protein E3L, the induction of apoptosis in nonpermissive HeLa cells requires free dsRNA and can be inhibited by hetorologous proteins that bind and sequester dsRNA.
85. Shors T, Kibler KV, Perkins KB, Seidler-Wulff R, Banaszak MP, Jacobs BL. Complementation of vaccinia virus deleted of the E3L gene by mutants of E3L. Virology. 239:1997;269-276.
86. Shors T, Jacobs BL. Complementation of deletion of the vaccinia virus E3L gene by the Escherichia coli RNase III gene. Virology. 227:1997;77-87.
87. McFadden G. Even viruses can learn to cope with stress. Science. 279:1998;40-41.
88. of outstanding interest Shisler JL, Senkevich TG, Berry MJ, Moss B. Ultraviolet-induced cell death blocked by a selonoprotein from a human dermatotropic poxvirus. Science. 279:1998;102-105 Although the role of oxidative stress as an inducer of apoptosis is well established, it has not been clear how viruses cope with reactive oxides and free radicals that are frequently encountered during virus infections. This paper is the first to show that a virus-encoded protein can scavenge these toxic reactants and prevent UV- or peroxide-induced apoptosis. This protein, from the poxvirus Molluscum contagiosum (MC066L), is also the first viral selenoprotein to be discovered.
89. s3 is required for protection from apoptosis induced by the virus. Proc Natl Acad Sci USA. 94:1997;7891-7896.
90. Whalen SG, Marcellus RC, Whalen A, Ahn NG, Ricciardi RP, Branton PE. Phosphorylation within the transactivation domain of adenovirus E1A protein by mitogen-activated protein kinase regulates expression of early region 4. J Virol. 71:1997;353-3545.
91. of outstanding interest Lavoie JN, Nguyen M, Marcellus RC, Branton PE, Shore GC. E4orf4, a novel adenovirus death factor that induces p53-independent apoptosis by a pathway that is not inhibited by zVAD-fmk. J Cell Biol. 140:1998;637-645 This paper was one of several showing that E4orf4 induces apoptosis in the absence of other viral proteins or p53, but this work also contains the observation that E4orf4-induced apoptosis is also distinct from the known caspase cascade, at least as defined by the inability to be inhibited by the broad-spectrum inhibitor zVAD-fmk. In fact, no cleavage of critical caspase substrates, such as CPP32 or PARP, was detected at all, suggesting the induction of a novel p53-independent apoptosis pathway.
92. of outstanding interest Shtrichman R, Kleinberger T. Adenovirus type 5 E4 open reading frame 4 protein induces apoptosis in transformed cells. J Virol. 72:1998;2975-2982 As in the previous paper (reference [91]), these authors showed that E4orf4 induces apoptosis in eiher the presence or absence of p53. In this work, they also show that a mutant allele of E4orf4 that cannot bind the protein phosphatase-2A fails to induce apoptosis. They propose that altered phosphorylations of apoptosis regulators such as Bcl-2, Bad or the mitogen-activated protein kinases might contribute to the apoptosis induction.
93. of special interest Barry M, Hnatiuk S, Mossman K, Lee S-F, Boshkov L, McFadden G. The myxoma virus M-T4 gene encodes a novel RDEL-containing protein that is retained within the endoplasmic reticulum and is important for the productive infection of lymphocytes. Virology. 239:1997;360-377 This paper shows that the M-T4 protein expressed by myxoma virus is a critical virulence factor for myxomatosis in infected rabbits and that virus deleted for the gene this protein induces apoptosis in infected rabbit T cells. The presence of a carboxy-terminal RDEL sequence (using single-letter code for amino acids) in M-T4 caused the protein to be retrieved in the endoplasmic reticulum making M-T4 the first viral apoptosis modulator known to be localized strictly to this compartment of infected cells.
94. of special interest Ramsey-Ewing A, Moss B. Apoptosis induced by a postbinding step of vaccinia virus entry into Chinese hamster ovary cells. Virology. 242:1996;138-149 Vaccinia replicates in most cell types, except for CHO cells in which it induces an abortive infection associated with apoptosis induction. This paper shows that this apoptosis response is induced at a very early stage and did not require the synthesis of any viral proteins but could be blocked with an antibody to a virion surface protein. These results indicate that the virus adsorption step might directly trigger apoptosis, suggesting that the virion itself might function as a proapoptotic ligand for an unidentified cell surface receptor.
95. of special interest Galvan V, Roizman B. Herpes simplex virus 1 induces and blocks apoptosis at multiple steps during infection and protects cells from exogenous inducers in a cell-type-dependent manner. of special interest Proc Natl Acad Sci USA. 95:1996;3931-3936 As in the previous paper (reference [94]), these authors show that even in the absence of any viral gene expression, virus adsorption and uptake alone can induce apoptosis. In this paper, herpes simplex virus type 1 is shown to be capable of inducing an apoptotic response at early times, that is then inhibited at several levels in a cell-specific fashion.In fact, all apoptosis inducers tested, including TNF, anti-Fas antibody, ceramide or environmental stress, were blocked in cells productively infected by the virus.