Pneumotropic revertants derived from a pantropic mutant, F1-R, of Sendai virus.
Pneumotropic revertants derived from a pantropic mutant, F1-R, of Sendai virus.
复制标题
嗜肺回复体源自仙台病毒的泛嗜性突变体 F1-R。
DOI：
10.1016/0042-6822(91)90839-4
复制
发表时间：
1991
期刊：
影响因子：
3.7
通讯作者：
Seto,JT
中科院分区：
文献类型：
--
作者：
Tashiro,M;James,I;Karri,S;Wahn,K;Tobita,K;Klenk,HD;Rott,R;Seto,JT
Revenants是从仙台病毒F1-R的蛋白酶激活突变体中分离出来的，这种突变体会引起小鼠的全身感染。 F1 -R 的融合 (F) 糖蛋白易于被普遍存在的细胞蛋白酶激活裂解，因此导致小鼠泛向性 (Tashiro et W., 1988.Virology165, 577–583)。回复体恢复了野生型病毒的几种表型；它们需要外源胰蛋白酶来激活细胞培养物和小鼠非肺组织中的 F 蛋白，并且它们在小鼠中仅具有嗜神经性。另一方面，亡魂未改变的F1-R表型是极化上皮细胞中的双极出芽、基质蛋白的电泳迁移增强以及F蛋白的F2亚基中缺乏糖基化位点。回复体F基因的比较RNA序列分析表明，回复体F蛋白的可切割性降低是由于在靠近切割位点的残基115处预测的单氨基酸回复（Pro到Ser）的结果。因此，与F1-R的Pro-Lys和野生型病毒的Ser-Arg相比，revenant的切割位点的序列是Ser-Lys。结果表明，糖蛋白裂解性的增强（通常与副粘病毒 F 蛋白和流感病毒血凝素裂解位点内的多个碱性残基相关）也可以通过脯氨酸后的单个碱性氨基酸来确定。此外，与野生型病毒相比，亡灵对小鼠肺部存在的野生型病毒激活剂的敏感性较低，并且对该器官的致病性较低。这些结果提供了进一步的证据，表明宿主蛋白酶对F蛋白的蛋白水解激活是仙台病毒在小鼠中的器官趋向性和致病性的主要决定因素。其中一名亡魂也对温度敏感（ts）；核蛋白基因中的 is 损伤与 ts-f1 中发现的损伤相同，ts-f1 是 F1-R 的宿主范围突变体。
Revenants were isolated from the protease activation mutant of Sendai virus, F1-R, which causes a systemic infection in mice. The fusion (F) glycoprotein of F1 -R is susceptible to activation cleavage by ubiquitous cellular proteases and is thus responsible for pantropism in mice (Tashiro et W., 1988.Virology165, 577–583). The revertants regained several phenotypes of wild-type virus; they required exogenous trypsin for activation of the F protein in cell cultures and in nonpulmonary mouse tissues and they were exclusively pneurnotropic in mice. On the other hand, phenotypes of F1 -R that remained unchanged by the revenants were bipolar budding in polarized epithelial cells, enhanced electrophoretic migration of the matrix protein, and the lack of a glycosylation site in the F2subunit of the F protein. Comparative RNA sequence analysis of the F gene of the revertants revealed that the reduced cleavability of the F protein of the revenants was the result of the predicted single amino acid reversion (Pro to Ser) at residue 115 adjacent to the cleavage site. Thus the sequence at the cleavage site of the revenants was Ser-Lys compared with Pro-Lys for F1-R and Ser-Arg for wild-type virus. The results indicate that enhanced cleavability of the glycoprotein, a feature often associated with multiple basic residues within the cleavage site of paramyxovirus F proteins and influenza virus hemagglutinins, can also be determined by a single basic amino acid following proline. Additionally, the revenants were less susceptible to the activator for wild-type virus present in mouse lungs and less pathogenic for this organ than wild-type virus. These results provide further evidence that proteolytic activation of the F protein by host proteases is the primary determinant for organ tropism and pathogenicity of Sendai virus in mice. One of the revenants was also temperature sensitive (ts); the is lesion in the nucleoprotein gene was identical to that found in ts-f1, the is host range mutant from which F1-R was derived.