Divergent patterns of progression to AIDS after infection from the same source: Human immunodeficiency virus type 1 evolution and antiviral responses
Divergent patterns of progression to AIDS after infection from the same source: Human immunodeficiency virus type 1 evolution and antiviral responses
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DOI：
10.1128/jvi.71.6.4284-4295.1997
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发表时间：
1997-06-01
影响因子：
5.4
通讯作者：
Mullins, JI
中科院分区：
文献类型：
--
作者：
Liu, SL;Schacker, T;Mullins, JI
人类免疫缺陷病毒1型(HIV-1)感染者发展为艾滋病的速度由宿主和病毒之间一系列复杂的相互作用决定。在这里，我们评估了两名几乎同时感染HIV-1的男性患者的病毒学特性和宿主反应-其中一名患者在感染后不到两年内发展为艾滋病，另一名患者在感染后仍无症状。明显的中和抗体和细胞免疫反应明显，进展较慢的患者通常表现出更强和更广泛的反应，除了感染早期的细胞毒性T淋巴细胞反应。在获得的第一个样本中，在两个患者中都发现了几乎相同的同质病毒群体；然而，在快速进展的患者中也发现了第二个无关的HIV-I病毒群体。无法确定第二个人是来自另一个感染源，还是这两个人是从原始来源传播的。较慢进展者的病毒种群迅速翻转和多样化，而快速进展者的两个病毒种群的进化速度都要慢得多。此外，这些多样性背后的突变变化的特征似乎是不同的，在较慢的进行者中发展出多样化选择的倾向，而在快速进行者的两个群体中保持着对净化选择的互惠偏向。因此，作为HN复制标志的快速进化可能反映了宿主对新出现的病毒变异的强大抵抗力和更长的无症状感染时间。此外，快速进展与达到某种抗原多样性阈值后任何可察觉的免疫反应的崩溃无关，而是与未能推动这种多样化和在宿主内具有最佳复制能力的变体相对不受阻碍地扩展有关。
The rate of progression to AIDS in human immunodeficiency virus type 1 (HIV-1)-infected individuals is determined by a complex series of interactions between the host and virus. Here we evaluate virologic properties and host responses in two men near-simultaneously infected with HIV-1 from the same sexual partner-one individual progressed to AIDS in less than 2 years, and the other remains asymptomatic 3 Sears postinfection. Distinct neutralizing antibody and cellular immune responses were evident, with the slower progressor exhibiting generally stronger and broader responses, except for cytotoxic T-lymphocyte responses early in infection. Virtually identical, homogeneous virus populations were found in both patients in the first sample obtained; however, a second unrelated HIV-I virus population was also found in the fast progressor. Whether the second population emanated from an additional source of infection or the two were transmitted from the original source could not be determined. The virus population in the slower progressor turned over and diversified rapidly, whereas both virus populations in the rapid progressor evolved at a much slower rate. In addition, the character of mutational changes underlying these diversities appeared to be distinct, with a bias for diversifying selection developing in the slower progressor and a reciprocal bias towards purifying selection maintained in both populations in the fast progressor. Thus, the rapid evolution that is a hallmark of HN replication may be a reflection of strong host resistance against emerging virus variants and a longer period of asymptomatic infection. Furthermore, rapid progression was not linked to a collapse of any appreciable immune response following attainment of some threshold of antigenic diversity but rather to a failure to drive this diversification and a condition of relatively unimpeded expansion of variants with optimized replicative capacity within the host.