Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection
Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection
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DOI：
10.1128/jvi.73.12.10489-10502.1999
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发表时间：
1999-12-01
影响因子：
5.4
通讯作者：
Mullins, JI
中科院分区：
文献类型：
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作者：
Shankarappa, R;Margolick, JB;Mullins, JI
为了了解原发性人类免疫缺陷病毒1型（HIV-1）感染和艾滋病发展之间无症状间隔的高度变异性，我们研究了9名中度或缓慢疾病进展的男性HIV-1 env基因C2-V5区域和T细胞亚群的演变。他们从血清转换的时间进行了监测，为期6至12年，直到发展为先进的疾病在7名男子。基于与创始毒株的病毒差异、连续时间点内的病毒群体多样性以及能够利用CXCR-1受体的病毒的生长分析，（X4病毒），在无症状间隔内存在三个不同的阶段：一个持续时间可变的早期阶段，在此期间线性增加（约1%/年），中间阶段平均持续1.8年，其特征是趋异度持续增加，但多样性趋于稳定或下降;后期阶段的特征是发散减缓或稳定，多样性持续稳定或下降。X4变异体在早期至中期相转变的时间附近出现，然后达到峰值代表性，并在中期和晚期相之间的转变附近开始下降。晚期相转变还与T细胞稳态的失败（由CD 3（+）T细胞的向下拐点定义）和CD 4（+）T细胞下降至小于或等于200个细胞/μ l相关。病毒分化和多样性、病毒辅助受体特异性和T细胞稳态和亚群组成之间的这些时间关联的强度支持以下概念：所述阶段代表中度进展者中HIV-1感染过程中病毒进化的一致模式，对这种模式的认识可能有助于解释以前关于病毒进化和疾病进展之间关系的相互矛盾的数据，为评估未经治疗和经治疗的HIV-1感染的免疫损伤和恢复提供了有用的框架。
To understand the high variability of the asymptomatic interval between primary human immunodeficiency virus type 1 (HIV-1) infection and the development of AIDS, we studied the evolution of the C2-V5 region of the HIV-1 env gene and of T-cell subsets in nine men with a moderate or slow rate of disease progression. They were monitored from the time of seroconversion for a period of 6 to 12 years until the development of advanced disease in seven men. Based on the analysis of viral divergence from the founder strain, viral population diversity within sequential time points, and the outgrowth of viruses capable of utilizing the CXCR-1 receptor (X4 viruses), the existence of three distinct phases within the asymptomatic interval is suggested: an early phase of variable duration during which linear increases (similar to 1% per year) in both divergence and diversity were observed; an intermediate phase lasting an average of 1.8 years, characterized by a continued increase in divergence but with stabilization or decline in diversity; and a late phase characterized by a slowdown or stabilization of divergence and continued stability or decline in diversity. X4 variants emerged around the time of the early- to intermediate-phase transition and then achieved peak representation and began a decline around the transition between the intermediate and late phases, The late-phase transition was also associated with failure of T-cell homeostasis (defined by a downward inflection in CD3(+) T cells) and decline of CD4(+) T cells to less than or equal to 200 cells/mu l. The strength of these temporal associations between viral divergence and diversity, viral coreceptor specificity, and T-cell homeostasis and subset composition supports the concept that the phases described represent a consistent pattern of viral evolution during the course of HIV-1 infection in moderate progressors, Recognition of this pattern may help explain previous conflicting data on the relationship between viral evolution and disease progression and may provide a useful framework for evaluating immune damage and recovery in untreated and treated HIV-1 infections.