Analysis of dominant-negative effects of mutant Env proteins of human immunodeficiency virus type 1
Analysis of dominant-negative effects of mutant Env proteins of human immunodeficiency virus type 1
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DOI：
10.1006/viro.2001.0944
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发表时间：
2001-07-20
期刊：
影响因子：
3.7
通讯作者：
Sakai, H
中科院分区：
文献类型：
--
作者：
Iwatani, Y;Kawano, K;Sakai, H
人类免疫缺陷病毒1型的Env蛋白被组装成一个稳定的三聚体，寡聚化是维持病毒传染性所必需的。Env的这一特性表明，Env突变体可能对病毒的感染性具有显性负向作用。为了研究这种可能性，我们建立了一个包装细胞系，其中野生型和突变型Env蛋白可以在单个细胞中同时表达。我们分析了两种类型的Env突变体的影响：细胞质尾部截断的TM突变体和gp120/gp41切割缺陷的突变体。发现细胞质尾部截断的蛋白与野生型TM形成寡聚体，并与病毒粒子结合，但不抑制野生型功能。相比之下，卵裂缺陷的Env与野生型蛋白的表型混合引起了显著的传染性抑制，表明该突变体具有很强的显性-阴性表型。(C) 2001学术出版社。
The Env protein of human immunodeficiency virus type 1 is assembled into a stable trimer, and oligomerization is required for maintenance of viral infectivity. This property of Env suggests that Env mutants may have a dominant-negative effect on virus infectivity. To investigate this possibility, we established a packaging cell line in which both wild-type and mutant Env proteins could be expressed simultaneously in a single cell. We analyzed the effects of two types of Env mutants: cytoplasmic tail-truncated TM mutants and a mutant defective in gp120/gp41 cleavage. The cytoplasmic tail-truncated proteins were found to be incorporated into virions by forming an oligomer with wild-type TM, but could not inhibit the wild-type function. In contrast, phenotypic mixing of cleavage-defective Env with the wild-type protein caused dramatic inhibition of infectivity, indicating that this mutant has a strong dominant-negative phenotype. (C) 2001 Academic Press.