EVOLUTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEF AND LONG TERMINAL REPEAT SEQUENCES OVER 4 YEARS INVIVO AND INVITRO
EVOLUTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NEF AND LONG TERMINAL REPEAT SEQUENCES OVER 4 YEARS INVIVO AND INVITRO
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DOI：
10.1128/jvi.65.1.225-231.1991
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发表时间：
1991-01-01
影响因子：
5.4
通讯作者：
WAINHOBSON, S
中科院分区：
文献类型：
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作者：
DELASSUS, S;CHEYNIER, R;WAINHOBSON, S
人类免疫缺陷病毒1型（HIV-1）基因组编码nef开放阅读框和长末端重复序列U3/R元件的851 bp片段的进化已经在体内和体外进行了4年的跟踪研究。通过对克隆聚合酶链反应产物进行测序，建立了任意时间的病毒序列种群。所研究的样本来自于先前对该基因进行详细分析的同一个人（a . Meyerhans， R. Cheynier， J. Albert， M. Seth， S. Kwok， J. Sninsky， L. Morfeldt-Manson， B. Asjö， and S. Wain-Hobson, Cell 58:901-910, 1989）。再一次，离体培养导致了次要形式的选择。在体内4年的时间里，没有明显的选择或生长出任何特定的U3/R序列。很少有缺陷的nef蛋白序列被观察到，这反驳了nef作为负调控因子的观点。虽然没有发现功能缺陷的启动子/反式激活响应元件，但反式激活效率在对照的0.2到2倍之间变化。编码最有效的反式激活响应区域的序列并没有超过其他序列。无论在体内还是在体外，该位点不同样本的极端遗传异质性表明，不存在单一的、独特的HIV序列。这表明不同的HIV-1基因座是独立进化的，重组是它们解耦的原因。
The evolution of an 851-bp segment of the human immunodeficiency virus type 1 (HIV-1) genome encoding the nef open reading frame and U3/R elements of the long terminal repeat has been followed over a 4-year period in vivo and in vitro. The population of viral sequences at any given time was established by sequencing cloned polymerase chain reaction products. The samples studied were derived from the same man for whom a detailed analysis of the tat gene was previously described (A. Meyerhans, R. Cheynier, J. Albert, M. Seth, S. Kwok, J. Sninsky, L. Morfeldt-Manson, B. Asjö, and S. Wain-Hobson, Cell 58:901-910, 1989). Once again in vitro culture resulted in the selection of minor forms. Over a 4-year period in vivo, there was no obvious selection for, or outgrowth of, any particular nef or U3/R sequence. Few defective nef protein sequences were observed, which argues against nef acting as a negative regulatory factor. Although no functionally defective promoter/trans-activation-responsive elements were identified, the transactivation efficiencies varied between 0.2 and 2 times that of the control. The sequence encoding the most efficient trans-activation-responsive region did not outgrow others. The extreme genetic heterogeneity of the different samples of the locus, either in vivo or in vitro, indicates that there is no such thing as a single, distinct HIV sequence. It is suggested that different HIV-1 loci evolve independently, recombination being responsible for their uncoupling.