Blocked early-stage latency in the peripheral blood cells of certain individuals infected with human immunodeficiency virus type 1.

Blocked early-stage latency in the peripheral blood cells of certain individuals infected with human immunodeficiency virus type 1.
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阻断某些感染 1 型人类免疫缺陷病毒的个体外周血细胞的早期潜伏期。

DOI:
10.1073/pnas.89.22.10663
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发表时间:
1992
影响因子:
11.1
通讯作者:
Pomerantz,RJ
Pomerantz,RJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Seshamma,T;Bagasra,O;Trono,D;Baltimore,D;Pomerantz,RJ

文献摘要

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人类免疫缺陷病毒1型(HIV-1)感染具有自然史,其特征在于可变但通常缓慢进展为免疫缺陷状态。我们已经描述了HIV-1前病毒潜伏在某些细胞系中的分子模型,其特征在于极低或检测不到水平的未剪接的基因组HIV-1特异性RNA,但显着水平的多重剪接的HIV-1特异性RNA。我们已经利用了定量逆转录酶启动的聚合酶链反应,以测量各种HIV-1 RNA的水平在外周血单核细胞。在无症状个体中,多重剪接的HIV-1 RNA的中位水平显著高于未剪接的病毒RNA的中位水平。此外,HIV-1 RNA模式的特征是多剪接的病毒RNA比未剪接的病毒RNA至少多10倍,在无症状个体中比在获得性免疫缺陷综合征患者中明显更常见。我们认为,无症状的临床HIV-1感染的特点是在HIV-1感染的早期阶段阻断的HIV-1感染的外周血细胞的优势。这种病毒表达模式,我们称之为阻断早期潜伏期,可能构成某些HIV-1感染者中潜伏感染细胞的储存库。
Human immunodeficiency virus type 1 (HIV-1) infections of humans have a natural history characterized by a variable but usually slow progression to an immunodeficient state. We have described a molecular model of HIV-1 proviral latency in certain cell lines, characterized by extremely low or undetectable levels of unspliced genomic HIV-1-specific RNA but significant levels of multiply spliced HIV-1-specific RNA. We have utilized a quantitative reverse transcriptase-initiated polymerase chain reaction to measure the levels of various HIV-1 RNA species in peripheral blood mononuclear cells. The median level of multiply spliced HIV-1 RNA was dramatically higher than the median level of unspliced viral RNA in asymptomatic individuals. In addition, HIV-1 RNA patterns characterized by at least a 10-fold excess of multiply spliced to unspliced viral RNA were significantly more common in asymptomatic individuals than in patients with the acquired immunodeficiency syndrome. We suggest that asymptomatic clinical HIV-1 infection is characterized by a preponderance of HIV-1-infected peripheral blood cells blocked at an early stage of HIV-1 infection. This viral expression pattern, which we have called blocked early-stage latency, may constitute a reservoir of latently infected cells in certain HIV-1-infected persons.