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Biochimie. 2019 Sep 10. pii: S0300-9084(19)30264-0. doi: 10.1016/j.biochi.2019.09.006. [Epub ahead of print]
Role of host trypsin-type serine proteases and influenza virus-cytokine-trypsin cycle in influenza viral pathogenesis. Pathogenesis-based therapeutic options.
Kido H1, Takahashi E2, Kimoto T2.
Author information
1 Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan. Electronic address: kido@tokushima-u.ac.jp. 2 Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan.
Abstract
Influenza A virus (IAV) is one of the most common infectious pathogen and associated with significant morbidity and mortality. Although processing the IAV hemagglutinin (HA) envelope glycoprotein precursor is a pre-requisite for viral membrane fusion activity, viral entry and transmission, HA-processing protease is not encoded in the IAV genome and thus the cellular trypsin-type serine HA-processing proteases determine viral infectious tropism and viral pathogenicity. The initial process of IAV infection of the airway is followed by marked upregulation of ectopic trypsin in various organs and endothelial cells through the induction of various proinflammatory cytokines, and this process has been termed the "influenza virus-cytokine-trypsin" cycle. In the advanced stage of IAV infection, the cytokine storm induces disorders of glucose and lipid metabolism and the "metabolic disorders-cytokine" cycle is then linked with the "influenza virus-cytokine-trypsin" cycle, to advance the pathogenic process into energy crisis and multiple organ failure. Application of protease inhibitors and treatment of metabolic disorders that break these cycles and their interconnection is therefore a promising therapeutic approach against influenza. This review discusses IAV pathogenicity on trypsin type serine HA-processing proteases, cytokines, metabolites and therapeutic options.
Copyright ? 2019. Published by Elsevier B.V.
KEYWORDS:
cytokine; ectopic trypsin; hemagglutinin; influenza virus; multiple organ failure; pyruvate dehydrogenase kinase 4; trypsin-type serine processing protease
PMID: 31518617 DOI: 10.1016/j.biochi.2019.09.006
Role of host trypsin-type serine proteases and influenza virus-cytokine-trypsin cycle in influenza viral pathogenesis. Pathogenesis-based therapeutic options.
Kido H1, Takahashi E2, Kimoto T2.
Author information
1 Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan. Electronic address: kido@tokushima-u.ac.jp. 2 Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Kuramoto-cho 3-18-15, Tokushima, 770-8503, Japan.
Abstract
Influenza A virus (IAV) is one of the most common infectious pathogen and associated with significant morbidity and mortality. Although processing the IAV hemagglutinin (HA) envelope glycoprotein precursor is a pre-requisite for viral membrane fusion activity, viral entry and transmission, HA-processing protease is not encoded in the IAV genome and thus the cellular trypsin-type serine HA-processing proteases determine viral infectious tropism and viral pathogenicity. The initial process of IAV infection of the airway is followed by marked upregulation of ectopic trypsin in various organs and endothelial cells through the induction of various proinflammatory cytokines, and this process has been termed the "influenza virus-cytokine-trypsin" cycle. In the advanced stage of IAV infection, the cytokine storm induces disorders of glucose and lipid metabolism and the "metabolic disorders-cytokine" cycle is then linked with the "influenza virus-cytokine-trypsin" cycle, to advance the pathogenic process into energy crisis and multiple organ failure. Application of protease inhibitors and treatment of metabolic disorders that break these cycles and their interconnection is therefore a promising therapeutic approach against influenza. This review discusses IAV pathogenicity on trypsin type serine HA-processing proteases, cytokines, metabolites and therapeutic options.
Copyright ? 2019. Published by Elsevier B.V.
KEYWORDS:
cytokine; ectopic trypsin; hemagglutinin; influenza virus; multiple organ failure; pyruvate dehydrogenase kinase 4; trypsin-type serine processing protease
PMID: 31518617 DOI: 10.1016/j.biochi.2019.09.006