Reovirus σ3 Protein Limits Interferon Expression and Cell Death Induction.

Autor:	Roebke KE; Department of Biology, Indiana University, Bloomington, Indiana, USA., Guo Y; Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA., Parker JSL; Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA., Danthi P; Department of Biology, Indiana University, Bloomington, Indiana, USA pdanthi@indiana.edu.
Jazyk:	angličtina
Zdroj:	Journal of virology [J Virol] 2020 Oct 27; Vol. 94 (22). Date of Electronic Publication: 2020 Oct 27 (Print Publication: 2020).
DOI:	10.1128/JVI.01485-20
Abstrakt:	Induction of necroptosis by mammalian reovirus requires both type I interferon (IFN)-signaling and viral replication events that lead to production of progeny genomic double-stranded RNA (dsRNA). The reovirus outer capsid protein μ1 negatively regulates reovirus-induced necroptosis by limiting RNA synthesis. To determine if the outer capsid protein σ3, which interacts with μ1, also functions in regulating necroptosis, we used small interfering RNA (siRNA)-mediated knockdown. Similarly to what was observed in diminishment of μ1 expression, knockdown of newly synthesized σ3 enhances necroptosis. Knockdown of σ3 does not impact reovirus RNA synthesis. Instead, this increase in necroptosis following σ3 knockdown is accompanied by an increase in IFN production. Furthermore, ectopic expression of σ3 is sufficient to block IFN expression following infection. Surprisingly, the capacity of σ3 protein to bind dsRNA does not impact its capacity to diminish production of IFN. Consistent with this, infection with a virus harboring a mutation in the dsRNA binding domain of σ3 does not result in enhanced production of IFN or necroptosis. Together, these data suggest that σ3 limits the production of IFN to control innate immune signaling and necroptosis following infection through a mechanism that is independent of its dsRNA binding capacity. IMPORTANCE We use mammalian reovirus as a model to study how virus infection modulates innate immune signaling and cell death induction. Here, we sought to determine how viral factors regulate these processes. Our work highlights a previously unknown role for the reovirus outer capsid protein σ3 in limiting the induction of a necrotic form of cell death called necroptosis. Induction of cell death by necroptosis requires production of interferon. The σ3 protein limits the induction of necroptosis by preventing excessive production of interferon following infection. (Copyright © 2020 American Society for Microbiology.)
Databáze:	MEDLINE
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