Ivanova L, Le L, Schlesinger M J
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Virus Res. 1995 Dec;39(2-3):165-79. doi: 10.1016/0168-1702(95)00083-6.
Alphaviruses of the Togaviridae encode a small hydrophobic polypeptide of 55 amino acids, noted as the 6K protein, that is synthesized as part of a polyprotein containing the sequences of the two major transmembranal viral structural glycoproteins. Mutations, insertions and deletions in the 6K appear to selectively interfere with the final stages of virus assembly and budding, producing aberrant, multi-cored infectious viruses. In addition, some of these mutations were pleiotropic and much more inhibitory to virus formation. One of the latter, a substitution of alanine in the wild-type Sindbis virus 6K gene by arginine, has been studied further and shown to interfere with normal proteolytic processing of the polyprotein. Cells infected with this mutant but not the wild-type virus also displayed viral antigens in nuclear membranes and released fragments of membranes into the cell culture media. A revertant, obtained by enrichment for a faster growing strain, 'suppressed' these defects and genetic mapping showed that the arginine codon had been modified to encode a methionine. However, the sequence of the 6K protein in this revertant was not wild-type and the revertant was still defective in assembly as demonstrated by formation of aberrant particles. A complete restoration of wild-type particle formation for this revertant could be effected by modifying the E2 glycoprotein sequence.
披膜病毒科的甲病毒编码一种由55个氨基酸组成的小疏水多肽，称为6K蛋白，它作为一种多蛋白的一部分被合成，该多蛋白包含两种主要跨膜病毒结构糖蛋白的序列。6K中的突变、插入和缺失似乎选择性地干扰病毒组装和出芽的最后阶段，产生异常的、多核感染性病毒。此外，其中一些突变具有多效性，对病毒形成的抑制作用更强。后者之一，即野生型辛德毕斯病毒6K基因中的丙氨酸被精氨酸取代，已被进一步研究，并显示会干扰多蛋白的正常蛋白水解加工。感染这种突变体而非野生型病毒的细胞在核膜中也显示出病毒抗原，并将膜片段释放到细胞培养基中。通过富集生长更快的菌株获得的回复株“抑制”了这些缺陷，遗传图谱显示精氨酸密码子已被修饰以编码甲硫氨酸。然而，该回复株中6K蛋白的序列并非野生型，并且如异常颗粒的形成所示，该回复株在组装方面仍然存在缺陷。通过修饰E2糖蛋白序列，可以使该回复株完全恢复野生型颗粒的形成。
