title: [Host cellular proteases trigger the infectivity of the influenza virus in the airway and brain].
abstract: The pathogenesis of the influenza and Sendai viruses is primarily determined by host cellular trypsin-type processing proteases that activate viral fusion activity and infectivity. We isolated three secretory trypsin-type proteases from rat lungs, such as tryptase Clara, mini-plasmin, and ectopic anionic trypsin, candidates for the processing proteases of viral envelope glycoproteins. These enzymes specifically cleave the precursor of fusion glycoprotein hemagglutinin (HA) of influenza virus at Arg(325) and the F(0) of Sendai virus at Arg(116) in the consensus cleavage motif, Gln(Glu)-X-Arg, resulting in the induction of infectivity of these viruses. These proteases show different localization in the airway and susceptibility for the processing of various subtypes of influenza virus HA, suggesting that these processing proteases determine the viral pathogenicity. Influenza virus readily infects and replicates in the airway epithelial cells but occasionally replicates in the central nervous system, particularly in children below 5-6 years of age and Reye's syndrome patients. We found an invasion by a non-neurovirulent influenza virus in cerebral capillaries with progressive brain edema of mice having impaired mitochondrial fatty acid metabolism congenitally or posteriorly in the newborn period. In the brain of these mice, mini-plasmin, which potentiates viral-multiplication in vivo and destroys the blood-brain barrier, accumulated with virus antigen in the brain capillaries but only a little in the control mice without impaired mitochondrial fatty acid metabolism.
authors.affiliation: Institute for Enzyme Research, The University of Tokushima, Japan. kido@ier.tokushima-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamada
authors.forename: Yuushi
authors.initials: Y
authors.lastname: Okumura
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology / Q000821:virology; D002648:Child; D002675:Child, Preschool; D018792:Encephalitis, Viral / Q000821:virology*; D005227:Fatty Acids / Q000378:metabolism; D005341:Fibrinolysin / Q000502:physiology*; D015686:Gene Products, env / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000201:enzymology / Q000821:virology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009975:Orthomyxoviridae / Q000254:growth & development / Q000472:pathogenicity*; D009976:Orthomyxoviridae Infections / Q000821:virology*; D010446:Peptide Fragments / Q000502:physiology*; D051381:Rats; D012202:Reye Syndrome / Q000821:virology; D012697:Serine Endopeptidases / Q000502:physiology*; D014357:Trypsin / Q000502:physiology*; D053802:Tryptases
chemical_list: D005227:Fatty Acids; D015686:Gene Products, env; D010446:Peptide Fragments; C019493:miniplasmin; D012697:Serine Endopeptidases; C075431:tryptase Clara; D014357:Trypsin; D053802:Tryptases; D005341:Fibrinolysin