Purifying selection of CCR5-tropic human immunodeficiency virus type 1 variants in AIDS subjects that have developed syncytium-inducing, CXCR4-tropic viruses
Purifying selection of CCR5-tropic human immunodeficiency virus type 1 variants in AIDS subjects that have developed syncytium-inducing, CXCR4-tropic viruses
复制标题
DOI：
10.1099/vir.0.81722-0
复制
发表时间：
2006-05-01
影响因子：
3.8
通讯作者：
Martínez, MA
中科院分区：
文献类型：
--
作者：
Fernàndez, G;Llano, A;Martínez, MA
人类免疫缺陷病毒1型(HIV-1)感染是由使用CCR5共同受体进入的病毒变体(CCR5嗜性或R5变体)建立的，而使用CXCR4作为共同受体(CXCR4嗜性或X4变体)的病毒在大约50%的感染者的疾病发展过程中出现。X4变种在体外可能有更高的适合性，在HIV-1阳性的人中，它们的检测通常伴随着更快的T细胞耗尽和艾滋病的发病。本文研究了HIV-1包膜病毒V3-V5区序列变异与CD4T细胞数低于200个细胞的感染者R5和X4变异体的正选择压力与L(-1)的关系。在疾病晚期，遗传距离和CD4(+)细胞计数之间存在相关性。与X4变异体共存的R5变异体显著低于不存在X4变异体的受试者的R5变异体(P<；0(.)0001)。同样，X4变异体的多样性显著高于R5变异体(P<；0(.)0001)，尽管正选择下的残基在两个变异体中的分布模式相似。因此，X4和R5变异体都受到来自寄主的高选择压力。此外，同一对象中X4和R5变种之间的相互作用导致了对R5变种的纯化选择，R5变种只作为同质病毒种群存活下来。这些结果表明，来自X4表型样本的R5变异体具有高度的同质性和弱正向选择压力。相反，来自R5表型样本的R5变异体是高度异质性的，并受到正选择压力的影响。
Human immunodeficiency virus type 1 (HIV-1) infection is established by virus variants that use the CCR5 co-receptor for entry (CCR5-tropic or R5 variants), whereas viruses that use CXCR4 as co-receptor (CXCR4-tropic or X4 variants) emerge during disease progression in approximately 50% of infected subjects. X4 variants may have a higher fitness ex vivo and their detection is usually accompanied by faster T-cell depletion and the onset of AIDS in HIV-1-positive individuals. Here, the relationship between the sequence variation of the HIV-1 env V3-V5 region and positive selective pressure on R5 and X4 variants from infected subjects with CD4 T cell counts below 200 cells mu l(-1) was studied. A correlation was found between genetic distance and CD4(+) cell count at late stages of the disease. R5 variants that co-existed with X4 variants were significantly less heterogeneous than R5 variants from subjects without X4 variants (P < 0(.)0001). Similarly, X4 variants had a significantly higher diversity than R5 variants (P < 0(.)0001), although residues under positive selection had a similar distribution pattern in both variants. Therefore, both X4 and R5 variants were subjected to high selective pressures from the host. Furthermore, the interaction between X4 and R5 variants within the same subject resulted in a purifying selection on R5 variants, which only survived as a homogeneous virus population. These results indicate that R5 variants from X4 phenotype samples were highly homogeneous and under weakly positive selective pressures. In contrast, R5 variants from R5 phenotype samples were highly heterogeneous and subject to positive selective pressures.