Zhu G W, Mukherjee S, Sahni M, Narayan O, Stephens E B
Department of Microbiology, Molecular Genetics, and Immunology, Marion Merell Dow Laboratory for Viral Pathogenesis, University of Kansas Medical Center, Kansas City 66160-7240, USA.
Virology. 1996 Jun 15;220(2):522-9. doi: 10.1006/viro.1996.0342.
We analyzed the sequence of nef genes from different tissues of three rhesus macaques that had been infected with molecularly cloned SIVmac239 for 88 to 92 weeks. Comparison of the predicted amino acid sequences revealed that each macaque had selected out specific amino acid substitutions and that most of this variation (70%) was confined to four regions, amino acids 39 to 75, 90 to 105, 153 to 167, and 191 to 217, comprising 36% of the protein. The nef genes in these animals underwent extensive genetic variation with average nucleotide and amino acid substitution rates varying from 0.86 to 2.84% and 2.47 to 6.27%, respectively, although tissue-specific selection of nef variants occurred in only 1 of 14 tissues examined in this study. Comparison of the rate of nucleotide and amino acid substitutions in the nef genes to those previously reported in the env in the central nervous system (CNS) and lymph node (LN) revealed that the predicted amino acid substitution rates for Nef were much higher than for the gp120 region of env in the CNS and LN tissues for one macaque. In the two other macaques, the predicted amino acid substitution rates were similar between these two proteins in LN tissues, but the amino acid substitution rates in Nef were significantly higher than in the gp120 from the CNS. Comparison of the nucleotide substitutions in the region of overlap between the env and the nef revealed that approximately 83% of the nucleotide substitutions in this area resulted in a Nef amino acid sequence change, 26% of the nucleotide substitutions resulted in a gp41 amino acid change, and 9.5% of nucleotide substitutions resulted in amino acid sequence changes in both proteins, suggesting a preference for the selection of amino acid substitutions in the Nef in these animals. Our results indicate that in animals infected with SIVmac239 for prolonged periods, variation in the nef occurs at rates similar to or exceeding that observed for the env gene.
我们分析了三只恒河猴不同组织中nef基因的序列，这三只恒河猴感染分子克隆的SIVmac239已达88至92周。对预测的氨基酸序列进行比较后发现，每只猕猴都选择了特定的氨基酸替换，并且这种变异的大部分（70%）局限于四个区域，即氨基酸39至75、90至105、153至167和191至217，占该蛋白质的36%。这些动物体内的nef基因经历了广泛的遗传变异，平均核苷酸和氨基酸替换率分别在0.86%至2.84%和2.47%至6.27%之间，尽管在本研究检测的14个组织中只有1个出现了nef变异的组织特异性选择。将nef基因中的核苷酸和氨基酸替换率与先前报道的中枢神经系统（CNS）和淋巴结（LN）中env基因的替换率进行比较，发现对于一只猕猴，Nef预测的氨基酸替换率远高于CNS和LN组织中env的gp120区域。在另外两只猕猴中，LN组织中这两种蛋白质的预测氨基酸替换率相似，但Nef中的氨基酸替换率明显高于CNS中的gp120。对env和nef重叠区域的核苷酸替换进行比较发现，该区域约83%的核苷酸替换导致Nef氨基酸序列改变，26%的核苷酸替换导致gp41氨基酸改变，9.5%的核苷酸替换导致两种蛋白质的氨基酸序列都发生改变，这表明这些动物倾向于选择Nef中的氨基酸替换。我们的结果表明，在长期感染SIVmac239的动物中，nef的变异率与env基因相似或超过env基因。
