Garten W, Vey M, Ohuchi R, Ohuchi M, Klenk H D
Institut für Virologie, Philipps-Universität Marburg, Germany.
Behring Inst Mitt. 1991 Jul(89):12-22.
Factors determining cleavability of influenza virus hemagglutinin which is activated by ubiquitous cellular endoproteases were analysed by carrying out site-directed mutagenesis on the cloned hemaglutinin genes of strains A/FPV/Rostock/34 (subtype H7) and A/Port Chalmers/1/73 (subtype H3). Substitutions at the cleavage site of the H7 hemagglutinin indicate that the tetrapeptide Arg-X-Lys/Arg-Arg is the minimal consensus sequence recognized by the ubiquitous proteases. The H3 hemagglutinin also became susceptible to these enzymes, when additional arginines were inserted at the cleavage site. Three arginines were sufficient, when the carbohydrate was removed, whereas four additional arginines are needed when this carbohydrate was present, indicating that the accessibility of the cleavage motif is important for the protease. The appropriate localization of the basic cleavage motif within the amino acid sequence and the spatial structure of the hemagglutinin precursor is an additional prerequisite for cleavage.
通过对A/FPV/Rostock/34（H7亚型）和A/Port Chalmers/1/73（H3亚型）毒株的克隆血凝素基因进行定点诱变，分析了由普遍存在的细胞内蛋白酶激活的流感病毒血凝素的可裂解性决定因素。H7血凝素裂解位点的替换表明，四肽精氨酸-X-赖氨酸/精氨酸-精氨酸是普遍存在的蛋白酶识别的最小共有序列。当在裂解位点插入额外的精氨酸时，H3血凝素也变得易受这些酶的作用。去除碳水化合物时，三个精氨酸就足够了，而存在这种碳水化合物时则需要额外的四个精氨酸，这表明裂解基序的可及性对蛋白酶很重要。碱性裂解基序在氨基酸序列中的适当定位以及血凝素前体的空间结构是裂解的另一个先决条件。
