THE CYTOPLASMIC DOMAIN OF SIMIAN IMMUNODEFICIENCY VIRUS TRANSMEMBRANE PROTEIN MODULATES INFECTIVITY
THE CYTOPLASMIC DOMAIN OF SIMIAN IMMUNODEFICIENCY VIRUS TRANSMEMBRANE PROTEIN MODULATES INFECTIVITY
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DOI：
10.1128/jvi.63.10.4395-4403.1989
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发表时间：
1989-10-01
影响因子：
5.4
通讯作者：
SONIGO, P
中科院分区：
文献类型：
--
作者：
CHAKRABARTI, L;EMERMAN, M;SONIGO, P
猴免疫缺陷病毒（SIV）和人免疫缺陷病毒2型（HIV-2）的显著特征是env基因中存在无义突变，导致合成缺乏胞质结构域的截短跨膜蛋白。通过对SIVmac 142感染性分子克隆的突变，我们研究了胞质结构域的功能和env无义突变的意义。当无义密码子（TAG）被谷氨酰胺密码子（CAG）取代时，病毒感染HUT 78细胞的动力学明显延迟。这种负面影响在体外被反选择，因为缓慢表型的逆转经常发生。对一个回复突变体的测序显示，在原始突变的3个核苷酸5”处存在一个新的终止密码子。在起始终止密码子的3“端引入缺失或额外的无义突变并不改变SIV的感染性。相反，在终止密码子被CAG取代的克隆中引入的相同缺失或无义突变消除了感染性。这些结果表明，位于终止密码子3“的包膜结构域对于体外复制不是必需的。然而，SIV跨膜蛋白中该结构域的存在导致感染性降低。这种负面影响可能对应于体内感染期间控制病毒传播速率的功能。
A striking characteristic of the simian immunodeficiency virus (SIV) and of the human immunodeficiency virus type 2 (HIV-2) is the presence of a nonsense mutation in the env gene resulting in the synthesis of a truncated transmembrane protein lacking the cytoplasmic domain. By mutagenesis of an infectious molecular clone of SIVmac142, we investigated the function of the cytoplasmic domain and the significance of the env nonsense mutation. When the nonsense codon (TAG) was replaced by a glutamine codon (CAG), the virus infected HUT78 cells with markedly delayed kinetics. This negative effect was counterselected in vitro as reversion of the slow phenotype frequently occurred. The sequencing of one revertant revealed the presence of a new stop codon three nucleotides 5'' to the original mutation. Deletions or an additional nonsense mutation introduced 3'' to the original stop codon did not modify SIV infectivity. In contrast, the same deletions or nonsense mutation introduced in the clone in which the stop codon was replaced by CAG abolished infectivity. These results indicated that the envelope domain located 3'' to the stop codon is not necessary for in vitro replication. However, the presence of this domain in SIV transmembrane protein leads to a reduced infectivity. This negative effect might correspond to a function controlling the rate of spread of the virus during in vivo infection.