Scheid A, Hsu M, Choppin P W
Soc Gen Physiol Ser. 1980;34:119-30.
Interactions of paramyxoviruses with cell membranes are mediated by two virus-coded glycoproteins of the virus membrane: HN and F. The HN protein is responsible for the attachment of virions to the membrane of the target cell. The F protein mediates fusion between the virus membrane and the cell membrane, and this step is essential for the infection process as well as for the expression of other biological activities of paramyxoviruses, i.e., cell fusion and hemolysis. The activity of F is dependent on the proteolytic processing of a precursor (F0) to yield two disulfide-linked subunits (F1 and F2), and unless this cleavage occurs, the virions are inactive and not infectious. Viruses differ in their susceptibility to specific proteases, as demonstrated with Sendai virus and its protease activation (pa) mutants. Findings with these viruses indicate that the host range, tissue tropism, and the ability of paramyxoviruses to spread within a host and to cause disease are dependent on the availability of an appropriate protease capable of cleaving the viral glycoprotein. Experiments with reconstituted particles that contain purified F protein and phosphatidylcholine indicate that to be active the F protein must be inserted in a lipid bilayer, and that no other viral function is needed for the membrane fusion process. Attachment of the F-protein-containing particles to the target membrane is a prerequisite for fusion; however, this function can be supplied by wheat germ agglutinin as well as by the virus protein responsible for attachment of intact virus, i.e., HN. Studies on the structure of the paramyxovirus glycoproteins indicate that they are inserted with a hydrophobic region of the molecule in the lipid bilayer of the virus membrane. Analysis of the primary structure of the F protein at the cleavage site revealed striking sequence homology among three paramyxoviruses, indicating a requirement for cleavage at a sharply defined site and the importance of a specific primary sequence for biological activity. This region is highly hydrophobic, suggesting that it may interact with the lipid biylayer of the target cell membrane during virus penetration, cell fusion, or hemolysis. Further studies of this system should provide knowledge regarding the mechanisms involved in viral penetration and in membrane fusion in general.
HN和F。HN蛋白负责病毒粒子与靶细胞膜的附着。F蛋白介导病毒膜与细胞膜之间的融合，这一步骤对于感染过程以及副粘病毒其他生物学活性的表达（即细胞融合和溶血）至关重要。F的活性取决于前体（F0）的蛋白水解加工以产生两个二硫键连接的亚基（F1和F2），除非发生这种切割，病毒粒子无活性且无传染性。病毒对特定蛋白酶的敏感性不同，如仙台病毒及其蛋白酶激活（pa）突变体所示。这些病毒的研究结果表明，副粘病毒的宿主范围、组织嗜性以及在宿主体内传播和致病的能力取决于能够切割病毒糖蛋白的合适蛋白酶的可用性。用含有纯化F蛋白和磷脂酰胆碱的重组颗粒进行的实验表明，F蛋白要具有活性必须插入脂质双层中，并且膜融合过程不需要其他病毒功能。含F蛋白的颗粒附着于靶膜是融合的先决条件；然而，这种功能可以由麦胚凝集素以及负责完整病毒附着的病毒蛋白（即HN）提供。对副粘病毒糖蛋白结构的研究表明，它们通过分子的疏水区域插入病毒膜的脂质双层中。对F蛋白切割位点一级结构的分析揭示了三种副粘病毒之间惊人的序列同源性，表明在一个明确界定的位点进行切割的必要性以及特定一级序列对生物学活性的重要性。该区域高度疏水，表明它可能在病毒穿透、细胞融合或溶血过程中与靶细胞膜的脂质双层相互作用。对该系统的进一步研究应能提供有关病毒穿透和一般膜融合所涉及机制的知识。
