RIPK3 promotes adenovirus type 5 activity

Research output: Contribution to journalArticlepeer-review

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RIPK3 promotes adenovirus type 5 activity. / Weigert, Melanie; Binks, Alex; Dowson, Suzanne; Leung, Elaine Y. L.; Athineos, Dimitris; Yu, Xinzi; Mullin, Margaret; Walton, Josephine B.; Orange, Clare; Ennis, Darren; Blyth, Karen; Tait, Stephen W. G.; Mcneish, Iain A.

In: Cell death & disease, Vol. 8, 3206 , 13.12.2017.

Research output: Contribution to journalArticlepeer-review

Harvard

Weigert, M, Binks, A, Dowson, S, Leung, EYL, Athineos, D, Yu, X, Mullin, M, Walton, JB, Orange, C, Ennis, D, Blyth, K, Tait, SWG & Mcneish, IA 2017, 'RIPK3 promotes adenovirus type 5 activity', Cell death & disease, vol. 8, 3206 . https://doi.org/10.1038/s41419-017-0110-8

APA

Weigert, M., Binks, A., Dowson, S., Leung, E. Y. L., Athineos, D., Yu, X., Mullin, M., Walton, J. B., Orange, C., Ennis, D., Blyth, K., Tait, S. W. G., & Mcneish, I. A. (2017). RIPK3 promotes adenovirus type 5 activity. Cell death & disease, 8, [3206 ]. https://doi.org/10.1038/s41419-017-0110-8

Vancouver

Weigert M, Binks A, Dowson S, Leung EYL, Athineos D, Yu X et al. RIPK3 promotes adenovirus type 5 activity. Cell death & disease. 2017 Dec 13;8. 3206 . https://doi.org/10.1038/s41419-017-0110-8

Author

Weigert, Melanie ; Binks, Alex ; Dowson, Suzanne ; Leung, Elaine Y. L. ; Athineos, Dimitris ; Yu, Xinzi ; Mullin, Margaret ; Walton, Josephine B. ; Orange, Clare ; Ennis, Darren ; Blyth, Karen ; Tait, Stephen W. G. ; Mcneish, Iain A. / RIPK3 promotes adenovirus type 5 activity. In: Cell death & disease. 2017 ; Vol. 8.

Bibtex

@article{8abd2a09065f438e94731849a430abae,
title = "RIPK3 promotes adenovirus type 5 activity",
abstract = "Oncolytic adenoviral mutants infect human malignant cells and replicate selectively within them. This induces direct cytotoxicity that can also trigger profound innate and adaptive immune responses. However, the mechanism by which adenoviruses produce cell death remains uncertain. We previously suggested that type 5 adenoviruses, including the E1A CR2 deletion mutant dl922-947, might induce a novel form of programmed death resembling necroptosis. Here we have investigated the roles of core necrosis proteins RIPK1, RIPK3 and MLKL in the cytotoxicity of dl922-947 and other adenovirus serotypes. By electron microscopy, we show that dl922-947 induces similar necrotic morphology as TSZ treatment (TNF-α, Smac mimetic, zVAD.fmk). However, dl922-947-mediated death is independent of TNF-α signalling, does not require RIPK1 and does not rely upon the presence of MLKL. However, inhibition of caspases, specifically caspase-8, induces necroptosis that is RIPK3 dependent and significantly enhances dl922-947 cytotoxicity. Moreover, using CRISPR/Cas9 gene editing, we demonstrate that the increase in cytotoxicity seen upon caspase inhibition is also MLKL dependent. Even in the absence of caspase inhibition, RIPK3 expression promotes dl922-947 and wild-type adenovirus type 5 efficacy both in vitro and in vivo. Together, these results suggest that adenovirus induces a form of programmed necrosis that differs from classical TSZ necroptosis.",
keywords = "Molecular ecology, Transcriptomics, Microbial ecology",
author = "Melanie Weigert and Alex Binks and Suzanne Dowson and Leung, {Elaine Y. L.} and Dimitris Athineos and Xinzi Yu and Margaret Mullin and Walton, {Josephine B.} and Clare Orange and Darren Ennis and Karen Blyth and Tait, {Stephen W. G.} and Mcneish, {Iain A.}",
year = "2017",
month = dec,
day = "13",
doi = "10.1038/s41419-017-0110-8",
language = "English",
volume = "8",
journal = "Cell death & disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - RIPK3 promotes adenovirus type 5 activity

AU - Weigert, Melanie

AU - Binks, Alex

AU - Dowson, Suzanne

AU - Leung, Elaine Y. L.

AU - Athineos, Dimitris

AU - Yu, Xinzi

AU - Mullin, Margaret

AU - Walton, Josephine B.

AU - Orange, Clare

AU - Ennis, Darren

AU - Blyth, Karen

AU - Tait, Stephen W. G.

AU - Mcneish, Iain A.

PY - 2017/12/13

Y1 - 2017/12/13

N2 - Oncolytic adenoviral mutants infect human malignant cells and replicate selectively within them. This induces direct cytotoxicity that can also trigger profound innate and adaptive immune responses. However, the mechanism by which adenoviruses produce cell death remains uncertain. We previously suggested that type 5 adenoviruses, including the E1A CR2 deletion mutant dl922-947, might induce a novel form of programmed death resembling necroptosis. Here we have investigated the roles of core necrosis proteins RIPK1, RIPK3 and MLKL in the cytotoxicity of dl922-947 and other adenovirus serotypes. By electron microscopy, we show that dl922-947 induces similar necrotic morphology as TSZ treatment (TNF-α, Smac mimetic, zVAD.fmk). However, dl922-947-mediated death is independent of TNF-α signalling, does not require RIPK1 and does not rely upon the presence of MLKL. However, inhibition of caspases, specifically caspase-8, induces necroptosis that is RIPK3 dependent and significantly enhances dl922-947 cytotoxicity. Moreover, using CRISPR/Cas9 gene editing, we demonstrate that the increase in cytotoxicity seen upon caspase inhibition is also MLKL dependent. Even in the absence of caspase inhibition, RIPK3 expression promotes dl922-947 and wild-type adenovirus type 5 efficacy both in vitro and in vivo. Together, these results suggest that adenovirus induces a form of programmed necrosis that differs from classical TSZ necroptosis.

AB - Oncolytic adenoviral mutants infect human malignant cells and replicate selectively within them. This induces direct cytotoxicity that can also trigger profound innate and adaptive immune responses. However, the mechanism by which adenoviruses produce cell death remains uncertain. We previously suggested that type 5 adenoviruses, including the E1A CR2 deletion mutant dl922-947, might induce a novel form of programmed death resembling necroptosis. Here we have investigated the roles of core necrosis proteins RIPK1, RIPK3 and MLKL in the cytotoxicity of dl922-947 and other adenovirus serotypes. By electron microscopy, we show that dl922-947 induces similar necrotic morphology as TSZ treatment (TNF-α, Smac mimetic, zVAD.fmk). However, dl922-947-mediated death is independent of TNF-α signalling, does not require RIPK1 and does not rely upon the presence of MLKL. However, inhibition of caspases, specifically caspase-8, induces necroptosis that is RIPK3 dependent and significantly enhances dl922-947 cytotoxicity. Moreover, using CRISPR/Cas9 gene editing, we demonstrate that the increase in cytotoxicity seen upon caspase inhibition is also MLKL dependent. Even in the absence of caspase inhibition, RIPK3 expression promotes dl922-947 and wild-type adenovirus type 5 efficacy both in vitro and in vivo. Together, these results suggest that adenovirus induces a form of programmed necrosis that differs from classical TSZ necroptosis.

KW - Molecular ecology

KW - Transcriptomics

KW - Microbial ecology

U2 - 10.1038/s41419-017-0110-8

DO - 10.1038/s41419-017-0110-8

M3 - Article

VL - 8

JO - Cell death & disease

JF - Cell death & disease

SN - 2041-4889

M1 - 3206

ER -