Le S Y, Chen J H, Chatterjee D, Maizel J V
Division of Cancer Biology and Diagnosis, National Cancer Institute, Frederick, MD 21701.
Nucleic Acids Res. 1989 Apr 25;17(8):3275-88. doi: 10.1093/nar/17.8.3275.
Genetic variation during the course of infection of an individual is a remarkable feature of the acquired immune deficiency syndrome (AIDS) disease. This variation has been studied for the envelope protein encoding regions of seventeen different sequences from various isolates of human immunodeficiency virus (HIV) using multiple sequence comparison and calculation of variability. The open regions with little intramolecular base pairing in these envelope sequences are predicted by a recently developed statistical method. The minimum length L for a run of hypervariable sites, conserved sites, or open regions that gives significance at the 1% (or 0.1%) level is then determined by a scan statistical method. The results show that significant clusters of open regions predicted at the RNA levels correlate with significant clusters of hypervariable sites in the HIV envelope gene. Those significant genomic variations in HIVs seem to be manifested mainly in the extracellular portion of the envelope protein. Twelve potential antigenic determinants are predicted using an antigenic index method. Interestingly, the majority of the significant hypervariable regions in the exterior envelope protein (gp120) were predicted potential epitopes.
个体感染过程中的基因变异是获得性免疫缺陷综合征(艾滋病)的一个显著特征。利用多序列比对和变异性计算,对来自人类免疫缺陷病毒(HIV)不同分离株的17个不同序列的包膜蛋白编码区进行了研究。通过一种新开发的统计方法预测了这些包膜序列中分子内碱基配对较少的开放区域。然后通过扫描统计方法确定在1%(或0.1%)水平具有显著性的高变位点、保守位点或开放区域的连续片段的最小长度L。结果表明,在RNA水平预测的开放区域的显著簇与HIV包膜基因中的高变位点的显著簇相关。HIV中的那些显著基因组变异似乎主要表现在包膜蛋白的细胞外部分。使用抗原指数方法预测了12个潜在的抗原决定簇。有趣的是,包膜外蛋白(gp120)中的大多数显著高变区域被预测为潜在表位。