Kawaoka Y
Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
J Virol. 1991 Mar;65(3):1195-201. doi: 10.1128/JVI.65.3.1195-1201.1991.
The cleavability of the hemagglutinin (HA) molecule is related to the virulence of avian influenza A viruses, but its influence on human influenza virus strains is unknown. Two structural features are involved in the cleavage of avian influenza A virus HAs: a series of basic amino acids at the cleavage site and an oligosaccharide side chain in the near vicinity. The importance of these properties in the cleavability of a human influenza A virus (A/Aichi/2/68) HA was investigated by using mutants that contained or lacked an oligosaccharide side chain and had either four or six basic amino acids. All mutants except the one that contains a single mutation at the glycosylation site were cleaved, although not completely, demonstrating that a series of basic amino acids confers susceptibility to cellular cleavage enzymes among human influenza virus HAs. The mutants containing six basic amino acids at the cleavage site showed limited polykaryon formation upon exposure to low pH, indicating that cleavage was adequate to impart fusion activity to the HA. Deletion of the potential glycosylation site had no effect on the cleavability of these mutants; hence, the oligosaccharide side chain appears to have no role in human influenza virus HA cleavage. The inability to induce high cleavability in a human influenza A virus HA by insertion of a series of basic amino acids at the cleavage site indicates that other, as yet unidentified structural features are needed to enhance the susceptibility of these HAs to cellular proteases.
血凝素（HA）分子的可裂解性与甲型禽流感病毒的毒力相关，但它对人流感病毒株的影响尚不清楚。甲型禽流感病毒HA的裂解涉及两个结构特征：裂解位点处的一系列碱性氨基酸和附近的一个寡糖侧链。通过使用含有或缺乏寡糖侧链且具有四个或六个碱性氨基酸的突变体，研究了这些特性在甲型人流感病毒（A/爱知/2/68）HA可裂解性中的重要性。除了在糖基化位点含有单个突变的突变体外，所有突变体均被裂解，尽管不完全裂解，这表明一系列碱性氨基酸赋予了人流感病毒HA对细胞裂解酶的敏感性。在裂解位点含有六个碱性氨基酸的突变体在暴露于低pH时显示出有限的多核体形成，表明裂解足以赋予HA融合活性。潜在糖基化位点的缺失对这些突变体的可裂解性没有影响；因此，寡糖侧链似乎在人流感病毒HA裂解中没有作用。通过在裂解位点插入一系列碱性氨基酸无法在甲型人流感病毒HA中诱导高可裂解性，这表明需要其他尚未确定的结构特征来增强这些HA对细胞蛋白酶的敏感性。
