IMPORTANCE OF THE NEF GENE FOR MAINTENANCE OF HIGH VIRUS LOADS AND FOR DEVELOPMENT OF AIDS
IMPORTANCE OF THE NEF GENE FOR MAINTENANCE OF HIGH VIRUS LOADS AND FOR DEVELOPMENT OF AIDS
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DOI：
10.1016/0092-8674(91)90097-i
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发表时间：
1991-05-17
期刊：
影响因子：
64.5
通讯作者：
DESROSIERS, RC
中科院分区：
文献类型：
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作者：
KESTLER, HW;RINGLER, DJ;DESROSIERS, RC
当恒河猴感染一种在nef的第93位密码子处具有提前终止信号的克隆SIVmac239时，在该位置具有编码密码子的回复突变体迅速且普遍地在感染的动物中占主导地位。 这表明nef在体内的开放功能形式有很强的选择力。 虽然nef序列的缺失对病毒在培养细胞中的复制没有可检测的影响，但nef序列的缺失显著改变了病毒在感染恒河猴中的特性。 我们的研究结果表明，nef是需要在体内持续感染过程中维持高病毒载量和充分的病理潜力。 因此，nef应该成为抗病毒药物开发的靶点。 此外，nef缺失的病毒的特性提示了制备用于实验性疫苗测试的减毒活病毒株的方法。
When rhesus monkeys were infected with a form of cloned SIVmac239 having a premature stop signal at the 93rd codon of nef, revertants with a coding codon at this position quickly and universally came to predominate in the infected animals. This suggests that there are strong selective forces for open functional forms of nef in vivo. Although deletion of nef sequences had no detectable effect on virus replication in cultured cells, deletion of nef sequences dramatically altered the properties of virus in infected rhesus monkeys. Our results indicate that nef is required for maintaining high virus loads during the course of persistent infection in vivo and for full pathologic potential. Thus, nef should become a target for antiviral drug development. Furthermore, the properties of virus with a deletion in nef suggest a means for making live-attenuated strains of virus for experimental vaccine testing.