Viral FLIP blocks Caspase-8 driven apoptosis in the gut in vivo

Ruder B, Günther C, Stürzl M, Neurath M, Cesarman E, Ballon G, Becker C (2020)

Publication Type: Journal article

Publication year: 2020

Journal

PLoS ONE Public Library of Science

Book Volume: 15

Article Number: e0228441

Journal Issue: 1

DOI: 10.1371/journal.pone.0228441

Abstract

A strict cell death control in the intestinal epithelium is indispensable to maintain barrier integrity and homeostasis. In order to achieve a balance between cell proliferation and cell death, a tight regulation of Caspase-8, which is a key player in controlling apoptosis, is required. Caspase-8 activity is regulated by cellular FLIP proteins. These proteins are expressed in different isoforms (cFLIPlong and cFLIPshort) which determine cell death and survival. Interestingly, several viruses encode FLIP proteins, homologous to cFLIPshort, which are described to regulate Caspase-8 and the host cell death machinery. In the current study a mouse model was generated to show the impact of viral FLIP (vFLIP) from Kaposi's Sarcoma-associated Herpesvirus (KSHV)/ Human Herpesvirus-8 (HHV-8) on cell death regulation in the gut. Our results demonstrate that expression of vFlip in intestinal epithelial cells suppressed cFlip expression, but protected mice from lethality, tissue damage and excessive apoptotic cell death induced by genetic cFlip deletion. Finally, our model shows that vFlip expression decreases cFlip mediated Caspase-8 activation in intestinal epithelial cells. In conclusion, our data suggests that viral FLIP neutralizes and compensates for cellular FLIP, efficiently counteracting host cell death induction and facilitating further propagation in the host organism.

Authors with CRIS profile

Claudia Günther Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie Markus Neurath Lehrstuhl für Innere Medizin I Christoph Becker Professur für Molekulare Gastroenterologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Cooper University Hospital US United States (USA) (US) Weill Cornell Medicine US United States (USA) (US)

How to cite

APA:

Ruder, B., Günther, C., Stürzl, M., Neurath, M., Cesarman, E., Ballon, G., & Becker, C. (2020). Viral FLIP blocks Caspase-8 driven apoptosis in the gut in vivo. PLoS ONE, 15(1). https://doi.org/10.1371/journal.pone.0228441

MLA:

Ruder, Barbara, et al. "Viral FLIP blocks Caspase-8 driven apoptosis in the gut in vivo." PLoS ONE 15.1 (2020).

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