CCR5/Δccr5 Heterozygosity: A Selective Pressure for the Syncytium-Inducing Human Immunodeficiency Virus Type 1 Phenotype
CCR5/Δccr5 Heterozygosity: A Selective Pressure for the Syncytium-Inducing Human Immunodeficiency Virus Type 1 Phenotype
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CCR5/Δccr5 杂合性：合胞体诱导人类免疫缺陷病毒 1 型表型的选择压力
DOI：
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
V. Johnson
中科院分区：
文献类型：
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作者：
R. D’Aquila;L. Sutton;A. Savara;M. Hughes;V. Johnson
体内合胞体诱导 (SI) 表型 HIV-1（人类免疫缺陷病毒 1 型）延迟显性的机制尚不清楚。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 到替代辅助受体使用的转变的基础。在进入 AIDS 临床试验组方案 241 的中晚期患者中，SI 病毒表型在 CCRS/delta(ccr5) 杂合子（7/7，100%）中比 CCR5/CCR5 纯合子（29/88，33%；P < .001，Fisher 精确检验）更常见。其他特征在研究开始时没有因 CCR5 基因型而异，包括中值 CD4 细胞计数、血浆 RNA 水平和循环细胞中的感染性 HIV-1 滴度。这些数据表明，CCR5/delta(ccr5)杂合性降低了可用作HIV-1进入辅助受体的CCR5的细胞表面水平，是使用替代辅助受体的T细胞系嗜性病毒进化的选择压力。
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.