D'Aquila R T, Sutton L, Savara A, Hughes M D, Johnson V A
Massachusetts General Hospital, Harvard Medical School, Boston, USA.
J Infect Dis. 1998 Jun;177(6):1549-53. doi: 10.1086/515307.
Mechanisms underlying the delay in dominance of syncytium-inducing (SI) phenotype HIV-1 (human immunodeficiency virus type 1) in vivo are unknown. Both random mutational events and selective pressures operative only late in the disease process have been suggested to underlie the shift from CCR5 to alternative coreceptor usage. Among the moderately advanced patients who entered AIDS Clinical Trials Group protocol 241, SI viral phenotype was more common among CCRS/delta(ccr5) heterozygotes (7/7, 100%) than among CCR5/CCR5 homozygotes (29/88, 33%; P < .001, Fisher's exact test). Other characteristics did not differ at study entry by CCR5 genotype, including median CD4 cell counts, plasma RNA levels, and infectious HIV-1 titers in circulating cells. These data indicate that CCR5/delta(ccr5) heterozygosity, which decreases cell-surface levels of CCR5 available to serve as an HIV-1 entry coreceptor, is a selective pressure for evolution of T cell line-tropic viruses that use an alternative coreceptor.
合胞体诱导（SI）表型的HIV-1（人类免疫缺陷病毒1型）在体内优势延迟的潜在机制尚不清楚。随机突变事件和仅在疾病过程后期起作用的选择性压力都被认为是从CCR5使用向替代共受体使用转变的基础。在进入艾滋病临床试验组方案241的中度晚期患者中，SI病毒表型在CCR5/δ（ccr5）杂合子中（7/7，100%）比在CCR5/CCR5纯合子中（29/88，33%；P<0.001，Fisher精确检验）更常见。在研究开始时，其他特征按CCR5基因型没有差异，包括CD4细胞计数中位数、血浆RNA水平和循环细胞中感染性HIV-1滴度。这些数据表明，CCR5/δ（ccr5）杂合性降低了可作为HIV-1进入共受体的CCR5细胞表面水平，是使用替代共受体的T细胞系嗜性病毒进化的选择性压力。
