Kestler H W, Ringler D J, Mori K, Panicali D L, Sehgal P K, Daniel M D, Desrosiers R C
New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772.
Cell. 1991 May 17;65(4):651-62. doi: 10.1016/0092-8674(91)90097-i.
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.
当恒河猴感染了一种在nef基因第93个密码子处带有提前终止信号的克隆SIVmac239时，在这个位置带有编码密码子的回复株迅速且普遍地在受感染动物体内占据主导地位。这表明在体内，对于具有开放功能形式的nef存在强大的选择压力。尽管缺失nef序列对培养细胞中的病毒复制没有可检测到的影响，但缺失nef序列显著改变了病毒在受感染恒河猴体内的特性。我们的结果表明，nef对于在体内持续感染过程中维持高病毒载量以及充分发挥病理潜能是必需的。因此，nef应该成为抗病毒药物研发的靶点。此外，nef缺失的病毒特性提示了一种制备减毒活病毒株用于实验性疫苗测试的方法。
