Quantification of latent tissue reservoirs and total body viral load in HIV-1 Infection
Quantification of latent tissue reservoirs and total body viral load in HIV-1 Infection
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DOI：
10.1038/387183a0
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发表时间：
1997-05-08
期刊：
影响因子：
64.8
通讯作者：
Siliciano, RF
中科院分区：
文献类型：
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作者：
Chun, TW;Carruth, L;Siliciano, RF
HIV-1建立潜伏性感染CD 4（+）T细胞的能力可能使病毒持续存在，尽管免疫应答和抗逆转录病毒治疗。血浆中感染性病毒（1，2）和病毒RNA（3，4）以及感染细胞中感染性病毒（1）、病毒DNA（5-10）和病毒信使RNA种类（11-14）的测量结果均表明，HIV-1复制在整个感染过程中持续进行。不确定性仍然存在于感染的CD 4（+）T细胞的比例以及是否存在潜伏的病毒库。我们发现在感染的无症状阶段，潜伏感染的静息CD 4（+）T细胞与具有复制能力的整合前病毒（< 10（7）个细胞）的总身体负荷极低。HIV-1 DNA在静止和活化的CD 4（+）T细胞中最普遍的形式是全长、线性、未整合的形式，其不具有复制能力。即使在淋巴组织中的任何给定时间，整合的HIV-1 DNA仅存在于易感人群的一小部分中，包括静息和活化的CD 4（+）T细胞和巨噬细胞，感染仍在进行。
The capacity of HIV-1 to establish latent infection of CD4(+) T cells may allow viral persistence despite immune responses and antiretroviral therapy. Measurements of infectious virus(1,2) and viral RNA(3,4) in plasma and of infectious virus(1), viral DNA(5-10) and viral messenger RNA species(11-14) in infected cells all suggest that HIV-1 replication continues throughout the course of infection. Uncertainty remains over what fraction of CD4(+) T cells are infected and whether there are latent reservoirs for the virus. We show here that during the asymptomatic phase of infection there is an extremely low total body load of latently infected resting CD4(+) T cells with replication-competent integrated provirus (< 10(7) cells). The most prevalent form of HIV-1 DNA in resting and activated CD4(+) T cells is a full-length, linear, unintegrated form that is not replication competent. The infection progresses even though at any given time in the lymphoid tissues integrated HIV-1 DNA is present in only a minute fraction of the susceptible populations, including resting and activated CD4(+) T cells and macrophages.