You are here: Home :: Area NEM :: Life sciences :: Biochemistry

Trong Quang Le, Miki Kawachi, Hiroshi Yamada, Mayumi Shiota, Yuushi Okumura, Hiroshi Kido

Identification of trypsin I as a candidate for influenza A virus and Sendai virus envelope glycoprotein processing protease in rat brain

Keywords: brain capillaries, hippocampal neuronal cell, influenza A virus, processing protease, trypsin I

Extracellular cleavage of virus envelope fusion glycoprotein hemagglutinin (HA₀) by host trypsin-like proteases is a prerequisite for the infectivity and pathogenicity of human influenza A viruses and Sendai virus. The common epidemic influenza A viruses are pneumotropic, but occasionally cause encephalopathy or encephalitis, although the HA₀ processing enzyme in the brain has not been identified. In searching for the brain processing proteases, we identified a processing enzyme in rat brain that was inducible by infection with these viruses. The purified enzyme exhibited an apparent molecular mass of approximately 22 kDa on SDS-PAGE and the N-terminal amino acid sequence was consistent with that of rat pancreatic trypsin I. Its substrate specificities and inhibition profiles were the same as those of pancreatic trypsin I. In situ hybridization and immunohistochemical studies on trypsin I distribution revealed heavy deposits in the brain capillaries, particularly in the allocortex, as well as in clustered neuronal cells of the hippocampus. The purified enzyme efficiently processed the HA₀ of human influenza A virus and the fusion glycoprotein precursor of Sendai virus. Our results suggest that trypsin I in the brain potentiates virus multiplication in the pathogenesis and progression of influenza-associated encephalopathy or encephalitis.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 387, 04/2006
Pages: 467 - 475

Show full article (external site)

Show all available items of this journal

 

Area NEM