{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:50:05Z","timestamp":1753883405369,"version":"3.41.2"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T00:00:00Z","timestamp":1719273600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"the Fundamental Research Funds for the Central Universities","award":["31920230163"],"award-info":[{"award-number":["31920230163"]}]},{"name":"the Undergraduate Innovation Project of Northwest Minzu University","award":["X202310742266"],"award-info":[{"award-number":["X202310742266"]}]},{"name":"the Project to Attract Foreign Experts","award":["G2022187005L"],"award-info":[{"award-number":["G2022187005L"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2024,6,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Mammalian orthoreovirus (MRV) outer capsid protein \u03c33 is a multifunctional protein containing a double-stranded RNA-binding domain, which facilitates viral entry and assembly. We reasoned that \u03c33 has an innate immune evasion function. Here, we show that \u03c33 protein localizes in the mitochondria and interacts with mitochondrial antiviral signaling protein (MAVS) to activate the intrinsic mitochondria-mediated apoptotic pathway. Consequently, \u03c33 protein promotes the degradation of MAVS through the intrinsic caspase-9\/caspase-3 apoptotic pathway. Moreover, \u03c33 protein can also inhibit the expression of the components of the RNA-sensing retinoic acid-inducible gene (RIG)-like receptor (RLR) signaling pathway to block antiviral type I interferon responses. Mechanistically, \u03c33 inhibits RIG-I and melanoma differentiation-associated gene 5 expression is independent of its inhibitory effect on MAVS. Overall, we demonstrate that the MRV \u03c33 protein plays a vital role in negatively regulating the RLR signaling pathway to inhibit antiviral responses. This enables MRV to evade host defenses to facilitate its own replication providing a target for the development of effective antiviral drugs against MRV.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>Mammalian orthoreovirus (MRV) is an important zoonotic pathogen, but the regulatory role of its viral proteins in retinoic acid-inducible gene-like receptor (RLR)-mediated antiviral responses is still poorly understood. Herein, we show that MRV \u03c33 protein co-localizes with mitochondrial antiviral signaling protein (MAVS) in the mitochondria and promotes the mitochondria-mediated intrinsic apoptotic pathway to cleave and consequently degrade MAVS. Furthermore, tryptophan at position 133 of \u03c33 protein plays a key role in the degradation of MAVS. Importantly, we show that MRV outer capsid protein \u03c33 is a key factor in antagonizing RLR-mediated antiviral responses, providing evidence to better unravel the infection and transmission mechanisms of MRV.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00236-24","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T13:01:27Z","timestamp":1715950887000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Mammalian orthoreovirus capsid protein \u03c33 antagonizes RLR-mediated antiviral responses by degrading MAVS"],"prefix":"10.1128","volume":"9","author":[{"given":"Dianyu","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou, China"},{"name":"Gansu Tech Innovation Center of Animal Cell, Biomedical Research 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