Glycoprotein D or J Delivered in<i>trans</i>Blocks Apoptosis in SK-N-SH Cells Induced by a Herpes Simplex Virus 1 Mutant Lacking Intact Genes Expressing Both Glycoproteins

Zhou, Guoying; Galván, Verónica; Campadelli-Fiume, Gabriella; Roizman, Bernard

doi:10.1128/jvi.74.24.11782-11791.2000

Cited by 132 publications

(142 citation statements)

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“…18,37,38 While it had been shown by this lab and others that wt HSV infection could block apoptosis induced by extracellular stimulants such as TNFa, anti-FAS antibody, CHX, STS, ceramide, osmotic shock using sorbitol or ethanol, and hyperthermia, 15,18,[37][38][39][40][41] we demonstrated that infected cell proteins produced during the apoptosis prevention window inhibited cell death triggered by STS and sorbitol. 15 Although most recent efforts have focused on identifying viral gene products involved in apoptosis prevention during infection, 15,17,18,37,[42][43][44] little is known of the mechanism of induction of the process. We are currently expanding our studies on apoptosis induction to include a diverse array of cells derived from various solid human tumors to extend our initial findings presented in this report.…”

Section: Discussionmentioning

confidence: 99%

Viral oncoapoptosis of human tumor cells

Aubert

Blaho

2003

Gene Ther

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Many cancer cells refractory to radiation treatment and chemotherapy proliferate because of loss of intrinsic programmed cell death (apoptosis) regulation. Consequently, the resolution of these cancers are many times outside the management capabilities of conventional therapeutics. We now report that replication-defective D27 herpes simplex virus (rd D27) triggers apoptosis in three representative transformed human cell lines. Susceptibility to virus-induced cell death is dependent on the abundance and distribution of modified p53 protein in the tumor cells indicating specific targeting of the treatment. Primary human and mouse fibroblast cells that produce modified p53 are resistant to rd D27 killing but not to apoptosis induced by nonviral environmental factors. These results suggest that induction of apoptosis by nonreplicating virus is a feasible genetic therapy approach for killing human cancer cells. Our findings may have important implications in designing novel virus-based anticancer strategies in appropriate animal model systems.

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Section: Discussionmentioning

confidence: 99%

Viral oncoapoptosis of human tumor cells

Aubert

Blaho

2003

Gene Ther

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“…This observation is consistent with recent studies published by other authors using different experimental models. In fact, Zhou et al (29,30) found that induction of HSV-1 gD expression in permissive SK-N-SH cells blocked apoptosis in cells infected with either gD (Ϫ/ϩ) or gD (Ϫ/Ϫ) virus, whereas Aubert et al (19) reported that accumulation of gD was associated with the inhibition of apoptosis by HSV-1. However, no evidence for prevention of apoptosis mediated by death receptors was reported by these authors.…”

Section: Discussionmentioning

confidence: 99%

“…At least one of the cell receptors for gD, namely herpesvirus entry mediator A (HveA; also known as HVEM, TNFRSF14), belongs to the family of tumor necrosis factor receptors, which play a central role in mediating signal transduction leading to death receptor-associated apoptosis (26 -28). Recent results have shown that gD delivered in trans blocks the apoptotic cascade triggered by HSV-1 mutants lacking the gene encoding gD in SK-N-SH cells (29,30). Cellular signals involved in the antiapoptotic action exerted by HSV-1-gD remain to be elucidated.…”

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confidence: 99%

Protection by Herpes Simplex Virus Glycoprotein D against Fas-mediated Apoptosis

Medici

Sciortino

Perri

et al. 2003

Journal of Biological Chemistry

106

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Signals involved in protection against apoptosis by herpes simplex virus 1 (HSV-1) were investigated. Using U937 monocytoid cells as an experimental model, we have demonstrated that HSV-1 rendered these cells resistant to Fas-induced apoptosis promptly after infection. UV-inactivated virus as well as the envelope glycoprotein D (gD) of HSV-1, by itself, exerted a protective effect on Fas-induced apoptosis. NF-B was activated by gD, and protection against Fas-mediated apoptosis by gD was abolished in cells stably transfected with a dominant negative mutant I-B␣, indicating that NF-B activation plays a role in the antiapoptotic activity of gD in our experimental model. Moreover, NF-B-dependent protection against Fas-mediated apoptosis was associated with decreased levels of caspase-8 activity and with the up-regulation of intracellular antiapoptotic proteins.Interest in the understanding of mechanisms by which viruses belonging to a variety of families regulate cell apoptosis has grown rapidly in recent years (1-3). Herpesviruses, due to the relatively large quantity of information contained in their genomes, seem particularly well equipped to exert a fine control over cell apoptosis (4). This occurs through various interactions among viral and cell products acting at different levels (5).Among herpesviruses, herpes simplex viruses have been shown to regulate apoptosis of infected cells both positively and negatively, according to the presence or absence of specific genes, experimental conditions, or specificity of target cells (6 -21).Glycoprotein D (gD) 1 is a main component of the external structure of HSV-1, and its function is essential for HSV-1 spread. Interaction between gD and cell receptors allows virion entry into cells to be infected (22)(23)(24)(25). At least one of the cell receptors for gD, namely herpesvirus entry mediator A (HveA; also known as HVEM, TNFRSF14), belongs to the family of tumor necrosis factor receptors, which play a central role in mediating signal transduction leading to death receptor-associated apoptosis (26 -28). Recent results have shown that gD delivered in trans blocks the apoptotic cascade triggered by HSV-1 mutants lacking the gene encoding gD in SK-N-SH cells (29,30). Cellular signals involved in the antiapoptotic action exerted by HSV-1-gD remain to be elucidated. Interestingly, overexpression of the gD receptor HveA has been shown to cause activation of the transcription factor, NF-B (28). Furthermore, it has been reported that engagement with HveA receptor of its natural ligand, LIGHT, can stimulate the activation of NF-B in different cellular systems (31,32). This suggests the possibility that also engagement of gD with HveA could lead to NF-B activation. The transcription factor NF-B consists of a homodimeric or heterodimeric complex of two subunits belonging to the highly conserved family of Rel-related proteins (33). The most important complex is that formed by two proteins with molecular masses of 50 kDa (p50) and 65 kDa (p65), respectively. This heterodimer is pre...

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“…Our laboratory reported that viral glycoprotein D, glycoprotein J, and the protein kinase encoded by the U S 3 gene each blocks apoptosis induced by replication-incompetent mutants or by proapoptotic cellular proteins such as BAD (1,5,8,9,14,15,17). Other studies added viral ribonucleotide reductase to the list of antiapoptotic viral proteins (18).…”

mentioning

confidence: 99%

Herpes simplex virus protein kinase U _S 3 activates and functionally overlaps protein kinase A to block apoptosis

Benetti

Roizman

2004

Proc. Natl. Acad. Sci. U.S.A.

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142

125

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Herpes simplex virus 1 encodes at least four genes whose functions include blocking apoptosis induced by exogenous agents (e.g., sorbitol, Fas ligand, and BAD protein) or replication-incompetent mutants (e.g., the d120 mutant lacking both copies of the ␣4 gene). U S3, one of these four genes, encodes a serine-threonine kinase that has been demonstrated to block apoptosis induced by proapoptotic cellular proteins or by the d120 mutant. The amino acid context of serine-threonine phosphorylated by U S3 is similar to that of the cAMP-dependent protein kinase PKA. We report that (i) the pattern of proteins phosphorylated by U S3 in transduced cells or in cells infected with WT virus overlaps that of phosphoproteins targeted by PKA, (ii) activation of PKA blocks apoptosis induced by d120 mutant or by BAD protein independently of U S3, (iii) US3 protein kinase phosphorylates peptides containing the serine or threonine targeted by PKA including that present in the regulatory type II␣ subunit of PKA, and (iv) in WT virus-infected cells the regulatory type II␣ subunit is phosphorylated in a US3-dependent manner. We conclude that a major determinant of the antiapoptotic activity of the U S3 protein kinase is the phosphorylation of PKA substrates by either or both enzymes.replication-defective viruses ͉ BAD protein ͉ forskolin ͉ RII␣ subunit of PKA

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Glycoprotein D or J Delivered intransBlocks Apoptosis in SK-N-SH Cells Induced by a Herpes Simplex Virus 1 Mutant Lacking Intact Genes Expressing Both Glycoproteins

Cited by 132 publications

References 39 publications

Viral oncoapoptosis of human tumor cells

Viral oncoapoptosis of human tumor cells

Protection by Herpes Simplex Virus Glycoprotein D against Fas-mediated Apoptosis

Herpes simplex virus protein kinase U _S 3 activates and functionally overlaps protein kinase A to block apoptosis

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Glycoprotein D or J Delivered intransBlocks Apoptosis in SK-N-SH Cells Induced by a Herpes Simplex Virus 1 Mutant Lacking Intact Genes Expressing Both Glycoproteins

Cited by 132 publications

References 39 publications

Viral oncoapoptosis of human tumor cells

Viral oncoapoptosis of human tumor cells

Protection by Herpes Simplex Virus Glycoprotein D against Fas-mediated Apoptosis

Herpes simplex virus protein kinase U S 3 activates and functionally overlaps protein kinase A to block apoptosis

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Product

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Herpes simplex virus protein kinase U _S 3 activates and functionally overlaps protein kinase A to block apoptosis