Rott R, Klenk H D, Nagai Y, Tashiro M
Institut für Virologie, Justus-Liebig-Universität Giessen, Germany.
Am J Respir Crit Care Med. 1995 Oct;152(4 Pt 2):S16-9. doi: 10.1164/ajrccm/152.4_Pt_2.S16.
Proteolytic cleavage of the influenza virus hemagglutinin glycoprotein (HA) by cellular proteases is a prerequisite for virus infectivity, spread of the virus in the infected organism, tissue tropism, and viral pathogenicity. Production of infectious virus depends upon the structure at the HA cleavage site as well as the substrate specificity and the distribution of appropriate enzymes. Differences exist in the specificities of the endoproteases that recognize the different sequence motifs at the cleavage site. With avian influenza viruses that cause lethal systemic infections, the cleavage site consists of multibasic amino acids. Furin, which activates this type of HA, is a member of the subtilisin family and represents the prototype of ubiquitously occurring membrane-bound proteases. On the other hand, serine proteases secreted from a restricted number of cell types and some bacterial enzymes recognize a monobasic cleavage signal at HA of the mammalian and the apathogenic avian influenza viruses. The limited occurrence of these proteases results in only localized infection. Implementation of these defined conditions for virus activation may represent a novel type of disease control.
细胞蛋白酶对流感病毒血凝素糖蛋白（HA）的蛋白水解切割是病毒感染性、病毒在受感染机体中的传播、组织嗜性和病毒致病性的先决条件。传染性病毒的产生取决于HA切割位点的结构以及底物特异性和合适酶的分布。识别切割位点不同序列基序的内切蛋白酶的特异性存在差异。对于引起致死性全身感染的禽流感病毒，切割位点由多个碱性氨基酸组成。激活这类HA的弗林蛋白酶是枯草杆菌蛋白酶家族的成员，是普遍存在的膜结合蛋白酶的原型。另一方面，从有限数量的细胞类型分泌的丝氨酸蛋白酶和一些细菌酶识别哺乳动物和无致病性禽流感病毒HA处的单碱性切割信号。这些蛋白酶的有限存在导致仅局部感染。实现这些确定的病毒激活条件可能代表一种新型的疾病控制方式。
