Multiple V1/V2 env variants are frequently present during primary infection with human immunodeficiency virus type
Multiple V1/V2 env variants are frequently present during primary infection with human immunodeficiency virus type
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DOI：
10.1128/jvi.78.20.11208-11218.2004
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发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Swanstrom, R
中科院分区：
文献类型：
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作者：
Ritola, K;Pilcher, CD;Swanstrom, R
人类免疫缺陷病毒1型(HIV-1)在慢性感染者中是一个由多种基因变异组成的复杂群体。然而，通过性传播的急性HIV-1感染是一种低概率事件，在这种情况下，最初接种被认为具有较低的遗传复杂性。为了评估HIV-1原发感染过程中存在的病毒复杂性，用能够分辨这些基因变异的异源双链跟踪试验(HTA)检测了env基因的V1/V2和V3可变区。对26名HIV-1原发感染者的血浆样本进行了多样性分析。一半的受试者在初次感染期间有一个以上的V1/V2病毒变异，这表明多个变异的频繁传播。这一观察结果与基于少量无细胞病毒传播接种的不频繁传播的想法不一致。在慢性感染者中，V1/V2和V3区病毒种群的复杂性甚至比急性感染者更大，这表明尽管在急性感染中存在多种变异，但病毒在传播过程中确实通过了遗传瓶颈。我们还使用HTA检查了感染病毒穿透不同解剖间隔的情况。在血浆中检测到的病毒变异与在精浆和/或脑脊液中检测到的病毒变异进行了比较。这些隔室中的病毒在很大程度上与血浆中的病毒相同，这一发现与感染变种的快速渗透一致(S)。多种变异的低概率传播可能是高传染性或过敏性的短暂时期的结果。或者，多重感染细胞的低效转移可能同时解释了低传播概率和多个变种的转移。
Human immunodeficiency virus type 1 (HIV-1) exists as a complex population of multiple genotypic variants in persons with chronic infection. However, acute HIV-1 infection via sexual transmission is a low-probability event in which there is thought to be low genetic complexity in the initial inoculum. In order to assess the viral complexity present during primary HIV-1 infection, the V1/V2 and V3 variable regions of the env gene were examined by using a heteroduplex tracking assay (HTA) capable of resolving these genotypic variants. Blood plasma samples from 26 primary HIV-1-infected subjects were analyzed for their level of diversity. Half of the subjects had more than one V1/V2 viral variant during primary infection, indicating the frequent transmission of multiple variants. This observation is inconsistent with the idea of infrequent transmission based on a small transmitting inoculum of cell-free virus. In chronically infected subjects, the complexity of the viral populations was even greater in both the V1/V2 and the V3 regions than in acutely infected subjects, indicating that in spite of the presence of multiple variants in acute infection, the virus does pass through a genetic bottleneck during transmission. We also examined how well the infecting virus penetrated different anatomical compartments by using the HTA. Viral variants detected in blood plasma were compared to those detected in seminal plasma and/or cerebral spinal fluid of six individuals. The virus in each of these compartments was to a large extent identical to virus in blood plasma, a finding consistent with rapid penetration of the infecting variant(s). The low-probability transmission of multiple variants could be the result of transient periods of hyperinfectiousness or hypersusceptibility. Alternatively, the inefficient transfer of a multiply infected cell could account for both the low probability of transmission and the transfer of multiple variants.