THE ROLE OF VESICULAR STOMATITIS-VIRUS MATRIX PROTEIN IN INHIBITION OF HOST-DIRECTED GENE-EXPRESSION IS GENETICALLY SEPARABLE FROM ITS FUNCTION IN VIRUS ASSEMBLY
THE ROLE OF VESICULAR STOMATITIS-VIRUS MATRIX PROTEIN IN INHIBITION OF HOST-DIRECTED GENE-EXPRESSION IS GENETICALLY SEPARABLE FROM ITS FUNCTION IN VIRUS ASSEMBLY
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DOI：
10.1128/jvi.67.8.4814-4821.1993
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发表时间：
1993-08-01
影响因子：
5.4
通讯作者：
LYLES, DS
中科院分区：
文献类型：
--
作者：
BLACK, BL;RHODES, RB;LYLES, DS
最近，已显示水泡性口炎病毒基质（M）蛋白能够在不存在其它病毒组分的情况下抑制宿主细胞定向转录（B. L. Black和D. S.莱尔斯，J. 66：4058-4064，1992）。M蛋白是一种主要的结构蛋白，已知其通过在出芽期间将病毒的螺旋核糖核蛋白核心结合到细胞质膜的细胞质表面而在病毒装配中发挥关键作用。在这项研究中，两个M蛋白突变体进行了测试，以确定是否由M蛋白的抑制宿主转录是一个间接的影响，其功能在病毒装配或是否代表一个独立的功能的M蛋白。条件性温度敏感性（TS）水泡性口炎病毒突变体tsO 82的突变M蛋白被发现在其抑制宿主定向基因表达的能力上有缺陷，如其不能抑制编码氯霉素乙酰转移酶的共转染靶基因的表达所示。tsO 82 M蛋白在病毒装配中发挥作用的能力与野生型M蛋白相似，如其补充III组ts M蛋白突变体tsO 23的能力所示。另一个突变体，MN 1，它缺乏M蛋白的氨基酸4至21表明，M蛋白抑制氯霉素乙酰转移酶基因的表达和本地化到细胞核的能力不受删除这个富含赖氨酸的氨基末端区域，但在病毒装配中发挥作用的能力被消融。因此，在这项研究中检查的两个M蛋白突变体表现出互补的表型：tsO 82 M蛋白在病毒组装中起作用，但在抑制宿主定向基因表达方面有缺陷，而MN 1 M蛋白在抑制基因表达方面起作用，但不能在病毒组装中起作用。这些数据表明，M蛋白在抑制宿主转录中的作用可以从其在病毒组装中的作用中遗传地分离。
Recently, the vesicular stomatitis virus matrix (M) protein has been shown to be capable of inhibition of host cell-directed transcription in the absence of other viral components (B. L. Black and D. S. Lyles, J. Virol. 66:4058-4064, 1992). M protein is a major structural protein that is known to play a critical role in virus assembly by binding the helical ribonucleoprotein core of the virus to the cytoplasmic surface of the cell plasma membrane during budding. In this study, two M protein mutants were tested to determine whether the inhibition of host transcription by M protein is an indirect effect of its function in virus assembly or whether it represents an independent function of M protein. The mutant M protein of the conditionally temperature-sensitive (ts) vesicular stomatitis virus mutant, tsO82, was found to be defective in its ability to inhibit host-directed gene expression, as shown by its inability to inhibit expression of a cotransfected target gene encoding chloramphenicol acetyltransferase. The ability of the tsO82 M protein to function in virus assembly was similar to that of wild-type M protein, as shown by its ability to complement the group III ts M protein mutant, tsO23. Another mutant, MN1, which lacks amino acids 4 to 21 of M protein demonstrated that the abilities of M protein to inhibit chloramphenicol acetyltransferase gene expression and to localize to the nucleus were unaffected by deletion of this lysine-rich amino-terminal region but that the ability to function in virus assembly was ablated. Thus, the two M protein mutants examined in this study exhibited complementary phenotypes: tsO82 M protein functioned in virus assembly but was defective in inhibition of host-directed gene expression, while MN1 M protein functioned in inhibiting gene expression but was unable to function in vims assembly. These data demonstrate that the role of M protein in inhibition of host transcription can be separated genetically from its role in virus assembly.