Michael N L, Chang G, d'Arcy L A, Tseng C J, Birx D L, Sheppard H W
Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland 20850, USA.
J Virol. 1995 Nov;69(11):6758-69. doi: 10.1128/JVI.69.11.6758-6769.1995.
We have studied the sequence and function of the human immunodeficiency virus type 1 (HIV-1) nef genes from nine patients with highly divergent rates of disease progression enrolled in a longitudinal study of HIV disease. Over an average of 7.8 years of follow-up, three patients had net positive changes in CD4+ T-cell counts, three patients had net negative changes in CD4+ T cells but did not develop AIDS, and three patients progressed to AIDS. The nef gene from each of these patients was amplified and cloned, and the sequence of 8 to 10 clones was determined. Only 2 of 88 (2.3%) nef genes recovered from these nine patients were grossly defective. Moreover, there was no relationship between the phylogeny of nef sequences and the corresponding rates of disease progression from these patients. Representative nef genes from all nine patients were tested for their abilities to downregulate cell surface CD4 in a transient-transfection assay. There was no correlation found between the functions of the nef genes from these patients and their corresponding rates of disease progression. We conclude that the nef gene is not a common mediator of the rate of HIV disease progression in natural infection.
我们研究了参与一项HIV疾病纵向研究的9例疾病进展速度差异很大的患者的1型人类免疫缺陷病毒（HIV-1）nef基因的序列和功能。在平均7.8年的随访期内，3例患者的CD4+T细胞计数有净增加，3例患者的CD4+T细胞有净减少但未发展为艾滋病，3例患者进展为艾滋病。对这些患者的每个nef基因进行了扩增和克隆，并测定了8至10个克隆的序列。从这9例患者中获得的88个nef基因中只有2个（2.3%）存在严重缺陷。此外，nef序列的系统发育与这些患者相应的疾病进展速度之间没有关系。在瞬时转染试验中测试了所有9例患者代表性nef基因下调细胞表面CD4的能力。这些患者的nef基因功能与其相应的疾病进展速度之间没有相关性。我们得出结论，nef基因不是自然感染中HIV疾病进展速度的常见介导因素。
