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The MAVS Immune Recognition Pathway in Viral Infection and Sepsis.
Sharma, Arjun; Kontodimas, Konstantinos; Bosmann, Markus.
  • Sharma A; Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
  • Kontodimas K; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
  • Bosmann M; Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
Antioxid Redox Signal ; 35(16): 1376-1392, 2021 12.
Article in English | MEDLINE | ID: covidwho-1342795
ABSTRACT

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 awaits better characterization in the future. New technical advances in multidimensional single-cell analysis and single-molecule methods will accelerate the rate of new discoveries. The ultimate goal is to manipulate MAVS activities in the form of immune-modulatory therapies to combat infections and sepsis. Antioxid. Redox Signal. 35, 1376-1392.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Diseases / Signal Transduction / Sepsis / Adaptor Proteins, Signal Transducing Limits: Animals / Humans Language: English Journal: Antioxid Redox Signal Journal subject: Metabolism Year: 2021 Document Type: Article Affiliation country: ARS.2021.0167

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Virus Diseases / Signal Transduction / Sepsis / Adaptor Proteins, Signal Transducing Limits: Animals / Humans Language: English Journal: Antioxid Redox Signal Journal subject: Metabolism Year: 2021 Document Type: Article Affiliation country: ARS.2021.0167