Goto H, Kawaoka Y
Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, 332 North Lauderdale, P.O. Box 318, Memphis, TN 38101, USA.
Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10224-8. doi: 10.1073/pnas.95.17.10224.
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.
蛋白酶对血凝素（HA）分子的切割是甲型流感病毒具有感染性的前提条件。在此，我们描述了1918年人类流感大流行毒株后代的HA切割新机制。我们证明，神经氨酸酶是病毒粒子表面的第二种主要蛋白质，它结合并隔离纤溶酶原，导致这种普遍存在的蛋白酶前体在局部浓度升高，从而增加HA的切割。神经氨酸酶分子这种异常功能的结构基础似乎是羧基末端赖氨酸的存在以及第146位（N2编号）缺乏寡糖侧链。这些发现提示了一种甲型流感病毒以及或许其他病毒也可能在人类中变得具有高致病性的方式。
