Passive sexual transmission of human immunodeficiency virus type 1 variants and adaptation in new hosts
Passive sexual transmission of human immunodeficiency virus type 1 variants and adaptation in new hosts
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DOI：
10.1128/jvi.02014-05
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发表时间：
2006-07-01
影响因子：
5.4
通讯作者：
Fidler, S.
中科院分区：
文献类型：
--
作者：
Frater, A. J.;Edwards, C. T. T.;Fidler, S.
人类免疫缺陷病毒1型（HIV-1）的遗传多样性是设计成功疫苗的主要障碍。某些病毒多态性编码人类白细胞抗原（HLA）相关的免疫逃逸，可能克服有限的疫苗保护。虽然免疫逃逸变异的传播已被报道，但这种现象在人群中发生的总体程度以及它对HIV-1病毒进化的贡献程度尚不清楚。HIV-1 env基因在传播时的选择有利于中和敏感的变异，但目前尚不清楚选择在多大程度上作用于HIV-1内部蛋白来限制或增强免疫逃逸变异的传播。研究表明HLA I类可能决定HIV-1感染的易感性，但HLA在传播中的明确作用仍未得到证实。比较急性血清转换者和慢性感染者的人群，我们没有发现选择限制HIV-1变异传播的证据。我们发现，以前在慢性感染中报道的病毒多态性和HLA I类等位基因之间的统计关联在急性感染中不存在，这表明这些患者中的大多数病毒多态性是传播而不是新生适应的结果。通过对四次HIV-1传播的研究，我们发现，尽管存在传播瓶颈，HIV-1感染的遗传变异仍以频率依赖的方式传播。由于HIV-1感染是由独特的供体适应病毒变体播种的，因此每次发作都是高度个体化的抗原挑战。宿主特异性、特异性HIV-1抗原多样性将严重影响基于共识序列的免疫效果。
Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design of a successful vaccine. Certain viral polymorphisms encode human leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited vaccine protection. Although transmission of immune escape variants has been reported, the overall extent to which this phenomenon occurs in populations and the degree to which it contributes to HIV-1 viral evolution are unknown. Selection on the HIV-1 env gene at transmission favors neutralization-sensitive variants, but it is not known to what degree selection acts on the internal HIV-1 proteins to restrict or enhance the transmission of immune escape variants. Studies have suggested that HLA class I may determine susceptibility to HIV-1 infection, but a definitive role for HLA at transmission remains unproven. Comparing populations of acute seroconverters and chronically infected patients, we found no evidence of selection acting to restrict transmission of HIV-1 variants. We found that statistical associations previously reported in chronic infection between viral polymorphisms and HLA class I alleles are not present in acute infection, suggesting that the majority of viral polymorphisms in these patients are the result of transmission rather than de novo adaptation. Using four episodes of HIV-1 transmission in which the donors and recipients were both sampled very close to the time of infection we found that, despite a transmission bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency-dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral variants, each episode is a highly individual antigenic challenge. Host-specific, idiosyncratic HIV-1 antigenic diversity will seriously tax the efficacy of immunization based on consensus sequences.