Direct cleavage of caspase-8 by herpes simplex virus 1 tegument protein US11.

Autor: Musarra-Pizzo M; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168, Messina, Italy. maria.musarrapizzo@unime.it., Pennisi R; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168, Messina, Italy., Lombardo D; Division of Clinical and Molecular Hepatology, University Hospital 'G. Martino' of Messina, 98124, Messina, Italy., Velletri T; IFOM-Cogentech Società Benefit Srl, via Adamello 16, 20139, Milan, Italy. Local Unit: Scientific and Technological Park of Sicily, 95121 Catania, Italy., Sciortino MT; Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168, Messina, Italy. mtsciortino@unime.it.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Jul 19; Vol. 12 (1), pp. 12317. Date of Electronic Publication: 2022 Jul 19.
DOI: 10.1038/s41598-022-15942-9
Abstrakt: The HSV-1 tegument protein Us11 counteracts the antiviral defense mechanisms by precluding the host protein shutoff. Previous works demonstrated that Us11 prevents heat-and staurosporine-induced apoptosis and inhibits autophagy. Therefore, in the present study, we investigated the hypothesis that HSV-1, through Us11, could recruit caspase-8, a key enzyme regulating programmed cell death. We first show that HSV-1 promotes the accumulation of caspase-8-p18 active fragments in both semi permissive THP-1 cells and fully permissive HEp-2 cells to HSV-1 replication. Using a recombinant virus R3630 (ΔUs11/ΔUs12) and a plasmid encoding Us11-recombinant protein we have proven that Us11 promotes p18 accumulation, which does not trigger the apoptotic signaling. Additional, in an in vitro model, we demonstrated that Us11-recombinant protein induces caspase-8-p18 cleavage by physically interacting with the caspase-8 recombinant protein. Finally, we found that, during HSV-1 replication, activated-caspase-8 cleaves Atg3 protein to potentially block autophagy and support its replication.
(© 2022. The Author(s).)
Databáze: MEDLINE
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