Mini-plasmin found in the epithelial cells of bronchioles triggers infection by broad-spectrum influenza A viruses and Sendai virus.
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. Here we report a protease present in the airway that, like tryptase Clara, can process influenza A virus haemagglutinin and Sendai virus envelope fusion glycoprotein. This protease was extracted from the membrane fraction of rat lungs, purified and then identified as a mini-plasmin. Mini-plasmin was distributed predominantly in the epithelial cells of the upward divisions of bronchioles and potentiated the replication of broad-spectrum influenza A viruses and Sendai virus, even that of the plasmin-insensitive influenza A virus strain. In comparison with plasmin, its increased hydrophobicity, leading to its higher local concentrations on membranes, and decreased molecular mass may enable mini-plasmin to gain ready access to the cleavage sites of various haemagglutinins and fusion glycoproteins after expression of these viral proteins on the cell surface. These findings suggest that mini-plasmin in the airway may play a pivotal role in the spread of viruses and their pathogenicity.
Murakami
M
M
Division of Enzyme Chemistry, Institute for Enzyme Research, University of Tokushima, Japan.
Towatari
T
T
Ohuchi
M
M
Shiota
M
M
Akao
M
M
Okumura
Y
Y
Parry
M A
MA
Kido
H
H
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000737:chemistry*; D005341:Fibrinolysin / Q000737:chemistry*; D006801:Humans; D007150:Immunohistochemistry; D007239:Infections; D009980:Influenza A virus / Q000378:metabolism*; D007531:Isoflurophate / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D018108:Respirovirus / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism
D010446:Peptide Fragments; D014759:Viral Envelope Proteins; C019493:miniplasmin; D007531:Isoflurophate; D005341:Fibrinolysin