Three Adenovirus E3 Proteins Cooperate to Evade Apoptosis by Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptor-1 and -2

Benedict, Chris A.; Norris, Paula S.; Prigozy, Theodore I.; Bodmer, Jean-Luc; Mahr, Jeffrey A.; Garnett, C. T.; Martinon, Fabio; Tschopp, Jürg; Gooding, Linda R.; Ware, Carl F.

doi:10.1074/jbc.m008218200

Cited by 119 publications

(109 citation statements)

References 47 publications

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“…38 For example, adenovirus EIB-19K, a Bcl-2 type protein, inhibits TNF-induced apoptosis by suppressing mitochondrial activation, 39,40 while the E3-10.4/14.5/6.7 proteins inhibit TRAIL-mediated apoptosis by decreasing the expression of DR4 and DR5 on the cell surface. 18 Bovine herpes virus-4 BORFE2 and equine herpes virus E8 prevent TNF and Fas-induced apoptosis by interfering with caspase 8 41,42 while CMV abrogates TNF, FasL and TRAIL-mediated apoptosis by suppressing the activation of caspase 8. 43 Our results provide substantive evidence that HPV 16 E6 targets procaspase 8 in order to block the transmission of apoptotic signals from TRAIL.…”

Section: Discussionmentioning

confidence: 99%

“…15 Alternatively, viruses may block death receptor signaling by interfering with one or more components of the signaling pathway. Exogenous HIV-1 tat has been shown to protect cells from TRAIL-mediated apoptosis, 16,17 as has the adenovirus E3-6.7K/10.4K/14.5K complex 18 and the human papillomavirus (HPV) 16 E5 protein. 19 All of these viral proteins inhibit TRAIL-induced cell death by targeting the TRAIL signaling cascade.…”

Section: Introductionmentioning

confidence: 99%

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Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis

2006

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Viruses have developed sophisticated strategies to evade host defenses and facilitate the production and spread of progeny. In this study, we show that transfection of the human papillomavirus (HPV) 16 E6 oncogene into HCT116 cells provides protection from tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. Additionally, we demonstrate that the protection provided by E6 is dose-dependent because higher levels of E6 provide greater protection. The mechanism underlying this protection involves a rapid reduction in the protein levels of both Fasassociated death domain (FADD) and procaspase 8, which results in suppression of the activation of caspases 8, 3 and 2. Interestingly, E6 does not interfere with the mitochondrial apoptotic pathway even though HCT116 cells have been classified as type II cells with regard to TRAIL signaling. These findings demonstrate that E6 has a more generalized effect on signaling by death ligands than was previously thought and support the notion that E6 can utilize p53-independent mechanisms to modulate cell survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis

2006

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“…40,41 Alternatively, as we show here, it can be addressed at least for some transgenes by an incomplete E3 deletion, which preserves some of the ORFs that encode polypeptides that interfere with activation of apoptosis pathway in packaging cell lines that express E1 in trans. 42,43 We assume that this prolongs the lifespan of the transduced packaging cells thus allowing for replicating Ad virus particles to mature before the cells die. Unfortunately, as we could not generate E1-and fully E3-deleted AdC vectors expressing gp140 or gp160, we were unable to pinpoint if indeed the reinserted E3 ORFs prevented premature apoptosis of the packaging cell lines.…”

Section: Discussionmentioning

confidence: 99%

A PartialE3Deletion in Replication-Defective Adenoviral Vectors Allows for Stable Expression of Potentially Toxic Transgene Products

Haut

Gill

Kurupati

et al. 2016

Human Gene Therapy Methods

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Adenovirus (Ad) is used extensively for construction of viral vectors, most commonly with deletion in its E1 and/or E3 genomic regions. Previously, our attempts to insert envelope proteins (Env) of HIV-1 into such vectors based on chimpanzee-derived Ad (AdC) viruses were thwarted. Here, we describe that genetic instability of an E1-and E3-deleted AdC vector of serotype C6 expressing Env of HIV-1 can be overcome by reinsertion of E3 sequences with anti-apoptotic activities. This partial E3 deletion presumably delays premature death of HEK-293 packaging cell lines due to Env-induced cell apoptosis. The same partial E3 deletion also allows for the generation of stable glycoprotein 140 (gp140)-and gp160-expressing Ad vectors based on AdC7, a distinct AdC serotype. Env-expressing AdC vectors containing the partial E3 deletion are genetically stable upon serial cell culture passaging, produce yields comparable to those of other AdC vectors, and induce transgene product-specific antibody responses in mice. A partial E3 deletion thereby allows expansion of the repertoire of transgenes that can be expressed by Ad vectors.Keywords: HIV-1, vaccine, genetic stability, immune responses INTRODUCTION REPLICATION-DEFECTIVE ADENOVIRUS (Ad) vectors efficiently deliver transgenes to multiple cell types. 1,2 They trigger a potent inflammatory response, 3,4 which initiates adaptive immune responses to the transgene product and the antigens of the Ad vector. 5 This has led to the development of different Ad serotypes as vaccine carriers for a plethora of antigens derived from viruses, 6-10 bacteria, 11,12 parasites, 13,14 or tumor cells, [15][16][17] which have consistently induced potent and sustained B and T cell responses to the transgene products.In most Ad vaccine vectors, the E1 and E3 domains are deleted from the genome. The E1 deletion renders Ad vectors replication defective and reduces synthesis of other Ad antigens. E3 encodes a number of polypeptides that have anti-apoptotic activity or allow the virus to escape immune surveillance. 18,19 The E3 domain, a region that is nonessential for viral replication, is generally deleted to allow for the insertion of lengthy transgene expression cassettes without exceeding the genome size of wild-type virus, as this could potentially result in genetic instability of Ad vectors. 20 Ad vectors have been explored extensively as vaccine carriers for antigens of human immunodeficiency virus (HIV)-1, 21-25 the causative agent of the acquired immunodeficiency syndrome (AIDS). While initial efforts focused on expression of internal antigens for the induction of CD8 + T cell responses against HIV-1, efforts have since shifted toward expression of the envelope protein (Env). The heavily glycosylated and highly variable Env of HIV-1 forms trimers composed of glycoprotein (gp) 120 and gp41 on the surface of the virion. These complexes allow HIV-1 to attach to its receptors and coreceptors and are thereby essential for CD4 + cell infection by HIV-1. Env is not only the sole target of HIV-1-specif...

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“…[45][46][47] The retention of these genes in TetON-TRAIL might be necessary for combining this vector with RC Ad in cancer cells that are highly sensitive to TRAIL-mediated apoptosis to prevent early death of the infected cells and to allow for a completion of the RC Ad infection cycle. Alternatively, the use of a weak promoter instead of an inducible promoter system for driving TRAIL expression might be sufficient for improvement of the oncolytic activity of an RC Ad in TRAIL-sensitive tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Anticancer activity of oncolytic adenovirus vector armed with IFN-α and ADP is enhanced by pharmacologically controlled expression of TRAIL

et al. 2007

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We have previously described oncolytic adenovirus (Ad) vectors KD3 and KD3-interferon (IFN) that were rendered cancer-specific by mutations in the E1A region of Ad; these mutations abolish binding of E1A proteins to p300/CBP and pRB. The antitumor activity of the vectors was enhanced by overexpression of the Adenovirus Death Protein (ADP, E3-11.6K) and by replication-linked expression of IFN-a. We hypothesized that the anticancer efficacy of the KD3-IFN vector could be further improved by expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). E1-deleted Ad vectors were constructed carrying reporter genes for enhanced green fluorescent protein or secreted placental alkaline phosphatase (SEAP) and a therapeutic gene for TRAIL under control of the TetON system. Expression of the genes was increased in the presence of a helper virus and the inducer doxycycline such that up to 231-fold activation of expression for the TetON-SEAP vector was obtained. Coinfection with TetON-TRAIL augmented oncolytic activity of KD3 and KD3-IFN in vitro. Induction of TRAIL expression did not reduce the yield of progeny virus. Combination of TetON-TRAIL and KD3-IFN produced superior antitumor activity in vivo as compared with either vector alone demonstrating the efficacy of a four-pronged cancer gene therapy approach, which includes Ad oncolysis, ADP overexpression, IFN-a-mediated immunotherapy, and pharmacologically controlled TRAIL activity.

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Three Adenovirus E3 Proteins Cooperate to Evade Apoptosis by Tumor Necrosis Factor-related Apoptosis-inducing Ligand Receptor-1 and -2

Cited by 119 publications

References 47 publications

Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis

Accelerated degradation of FADD and procaspase 8 in cells expressing human papilloma virus 16 E6 impairs TRAIL-mediated apoptosis

A PartialE3Deletion in Replication-Defective Adenoviral Vectors Allows for Stable Expression of Potentially Toxic Transgene Products

Anticancer activity of oncolytic adenovirus vector armed with IFN-α and ADP is enhanced by pharmacologically controlled expression of TRAIL

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