Kawaoka Y, Webster R G
Department of Virology and Molecular Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38101.
J Virol. 1989 Aug;63(8):3296-300. doi: 10.1128/JVI.63.8.3296-3300.1989.
The ability of many viruses to replicate in host cells depends on cleavage of certain viral glycoproteins, including hemagglutinin (HA). By generating site-specific mutant HAs of two highly virulent influenza viruses, we established that the relationship between carbohydrate in the stalk and the length of the connecting peptide is a critical determinant of cleavability. HAs that lacked an oligosaccharide side chain in the stalk were cleaved regardless of the number of basic amino acids at the cleavage site, whereas those with the oligosaccharide side chain resisted cleavage unless additional basic amino acids were inserted. This finding suggests that the oligosaccharide side chain interferes with HA cleavage if the number of basic amino acids at the cleavage site is not adequate to nullify this effect. Similar interplay could influence cleavage of other viral glycoproteins, such as those of human and simian immunodeficiency viruses and paramyxoviruses.
许多病毒在宿主细胞中复制的能力取决于某些病毒糖蛋白的裂解,包括血凝素(HA)。通过构建两种高致病性流感病毒的位点特异性突变HA,我们确定了柄部碳水化合物与连接肽长度之间的关系是可裂解性的关键决定因素。柄部缺乏寡糖侧链的HA无论裂解位点处碱性氨基酸的数量如何都会被裂解,而具有寡糖侧链的HA除非插入额外的碱性氨基酸否则会抵抗裂解。这一发现表明,如果裂解位点处碱性氨基酸的数量不足以抵消这种影响,寡糖侧链会干扰HA的裂解。类似的相互作用可能会影响其他病毒糖蛋白的裂解,例如人类和猿猴免疫缺陷病毒以及副粘病毒的糖蛋白。