A novel mechanism for the acquisition of virulence by a human influenza A virus

H Goto, Y Kawaoka - … of the National Academy of Sciences, 1998 - National Acad Sciences
H Goto, Y Kawaoka
Proceedings of the National Academy of Sciences, 1998National Acad Sciences
Cleavage of the hemagglutinin (HA) molecule by proteases is a prerequisite for the
infectivity of influenza A viruses. Here, we describe a novel mechanism of HA cleavage for a
descendant of the 1918 pandemic strain of human influenza virus. We demonstrate that
neuraminidase, the second major protein on the virion surface, binds and sequesters
plasminogen, leading to higher local concentrations of this ubiquitous protease precursor
and thus to increased cleavage of the HA. The structural basis of this unusual function of the …
Cleavage of the hemagglutinin (HA) molecule by proteases is a prerequisite for the infectivity of influenza A viruses. Here, we describe a novel mechanism of HA cleavage for a descendant of the 1918 pandemic strain of human influenza virus. We demonstrate that neuraminidase, the second major protein on the virion surface, binds and sequesters plasminogen, leading to higher local concentrations of this ubiquitous protease precursor and thus to increased cleavage of the HA. The structural basis of this unusual function of the neuraminidase molecule appears to be the presence of a carboxyl-terminal lysine and the absence of an oligosaccharide side chain at position 146 (N2 numbering). These findings suggest a means by which influenza A viruses, and perhaps other viruses as well, could become highly pathogenic in humans.
National Acad Sciences