Role of plasminogen-binding neuraminidase in influenza pathogenicity

Because hemagglutinin (HA) cleavage by proteases is a prerequisite for the infectivity of influenza A virus, it is a major determinant of viral pathogenicity. Although a mechanism by which HA cleavage plays a role in pathogenicity has been well studied in avian influenza viruses, in mammalian viruses it is not well understood. We demonstrated that the neuraminidase (NA) of a human isolate A/WSN/33, which is highly pathogenic in mice, bound and sequestered plasminogen, resulting in increased HA cleavability. To prove that plasminogen-binding activity of the NA determines the pathogenicity of influenza virus in mice, we generated mutant viruses that are deficient in plasminogen-binding activity by reverse genetics. (C) 2001 Elsevier Science B.V All rights reserved.