The MAVS Immune Recognition Pathway in Viral Infection and Sepsis

作者：Arjun Sharma, Konstantinos Kontodimas, Markus Bosmann · 发表于：Antioxidants and Redox Signaling · 年份：2021 · DOI：10.1089/ars.2021.0167 · 被引用次数：62 · 研究领域：interferon and immune responses、Immune Response and Inflammation、Mosquito-borne diseases and control

Significance: It is estimated that close to 50 million cases of sepsis result in over 11 million annual fatalities worldwide. The pathognomonic feature of sepsis is a dysregulated inflammatory response arising from viral, bacterial, or fungal infections. Immune recognition of pathogen-associated molecular patterns is a hallmark of the host immune defense to combat microbes and to prevent the progression to sepsis. Mitochondrial antiviral signaling protein (MAVS) is a ubiquitous adaptor protein located at the outer mitochondrial membrane, which is activated by the cytosolic pattern recognition receptors, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation associated gene 5 (MDA5), following binding of viral RNA agonists. Recent Advances: Substantial progress has been made in deciphering the activation of the MAVS pathway with its interacting proteins, downstream signaling events (interferon [IFN] regulatory factors, nuclear factor kappa B), and context-dependent type I/III IFN response. Critical Issues: In the evolutionary race between pathogens and the host, viruses have developed immune evasion strategies for cleavage, degradation, or blockade of proteins in the MAVS pathway. For example, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) M protein and ORF9b protein antagonize MAVS signaling and a protective type I IFN response. Future Directions: The role of MAVS as a sensor for nonviral pathogens, host cell injury, and metabolic perturbations awai...