Identification of ectopic anionic trypsin I in rat lungs potentiating pneumotropic virus infectivity and increased enzyme level after virus infection

• Published in: European journal of biochemistry Vol. 269; no. 10; pp. 2613 - 2621
• Main Authors: Towatari, Takae, Ide, Mikiko, Ohba, Kumiko, Chiba, Yuusuke, Murakami, Meiko, Shiota, Mayumi, Kawachi, Miki, Yamada, Hiroshi, Kido, Hiroshi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science, Ltd 01.05.2002
• Subjects: Amino Acid Sequence; Animals; anionic trypsin I; Enzyme Induction; influenza A virus; Lung - enzymology; Lung - virology; Lung Diseases - enzymology; Lung Diseases - virology; Male; Molecular Sequence Data; Pancreas - enzymology; processing protease; rat lung; Rats; Rats, Wistar; Respirovirus Infections - etiology; Respirovirus Infections - virology; Sendai virus; Sendai virus - physiology; Sequence Homology, Amino Acid; Substrate Specificity; Trypsin - isolation & purification; Trypsin - metabolism; Trypsin Inhibitors - pharmacology; Trypsinogen - metabolism
• ISSN: 0014-2956; 1432-1033
• DOI: 10.1046/j.1432-1033.2002.02937.x

Extracellular cleavage of virus envelope fusion glycoproteins by host cellular proteases is a prerequisite for the infectivity of mammalian and nonpathogenic avian influenza viruses, and Sendai virus. In search of such target processing proteases in the airway, we recently found a new candidate trypsin‐like processing protease in rat lungs, which was induced by Sendai virus infection, and identified as ectopic rat anionic trypsin I. On SDS/PAGE under reducing and nonreducing conditions, the purified enzyme gave protein bands corresponding to 29 and 22 kDa, respectively, i.e. at the same positions as rat pancreatic anionic trypsin I. It exhibited an apparent molecular mass of 31 kDa on molecular sieve chromatography and its isoelectric point was pH 4.7. The amino‐acid sequences of the N‐terminus and proteolytic digest peptides of the purified enzyme were consistent with those of rat pancreatic anionic trypsin I. Its substrate specificities and inhibitor sensitivities were the same as those of the pancreatic enzyme. The purified enzyme efficiently processed the fusion glycoprotein precursor of Sendai virus and hemagglutinin of human influenza A virus, and potentiated the infectivity of Sendai virus in the same dose‐dependent manner as the pancreatic one. Immunohistochemical studies revealed that this protease is located in the stromal cells in peri‐bronchiolar regions. These results suggest that ectopic anionic trypsin I in rat lungs induced by virus infection may trigger virus spread in rat lungs.