Human immunodeficiency virus type 1 mRNA expression in peripheral blood cells predicts disease progression independently of the numbers of CD4+ lymphocytes.
Human immunodeficiency virus type 1 mRNA expression in peripheral blood cells predicts disease progression independently of the numbers of CD4+ lymphocytes.
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外周血细胞中人类免疫缺陷病毒 1 型 mRNA 表达预测疾病进展，与 CD4 淋巴细胞数量无关。
DOI：
10.1073/pnas.91.3.1104
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发表时间：
1994
影响因子：
11.1
通讯作者：
Baltimore,D
中科院分区：
文献类型：
--
作者：
Saksela,K;Stevens,C;Rubinstein,P;Baltimore,D
为了阐明人类免疫缺陷病毒 (HIV) 在外周血单核细胞 (PBMC) 中复制的重要性，我们使用逆转录酶启动的 PCR 来测量在一项长期前瞻性研究中从一组 HIV 感染者收集的 PBMC 样本中 HIV-1 mRNA 的表达。我们发现临床和实验室指标非常相似的个体之间的 HIV mRNA 表达存在显着差异，并且这种差异与疾病的未来病程密切相关。在无症状个体的 PBMC 中未检测到病毒复制的证据，此后这些个体的 CD4+ 细胞水平至少保持正常 5 年。无论采样时 CD4+ 细胞数量是否正常，PBMC 中 HIV-1 mRNA 的丰富表达都预示着未来 2 年内疾病进展加速。因此，与其他病毒库（例如淋巴组织）中的 HIV 复制速率无关，PBMC 中的 HIV mRNA 量似乎反映了 HIV 疾病的后续发展。我们还使用逆转录酶启动的 PCR 测定来证明对 3'-叠氮基-3'-脱氧胸苷治疗的瞬时反应。因此，测定感染个体的 PBMC 中的 HIV-1 mRNA 表达可以作为预后指标以及作为指导和监测抗病毒治疗的手段具有重要的临床实用性。
To address the significance of human immunodeficiency virus (HIV) replication in peripheral blood mononuclear cells (PBMCs), we have used reverse transcriptase-initiated PCR to measure HIV-1 mRNA expression in PBMC specimens collected from a cohort of HIV-infected individuals during a long-term prospective study. We found dramatic differences in HIV mRNA expression among individuals with very similar clinical and laboratory indices, and this variation strongly correlated with the future course of the disease. No evidence of viral replication was detected in PBMCs from asymptomatic individuals who, thereafter, had normal levels of CD4+ cells for at least 5 years. Irrespective of whether the CD4+ cell numbers were normal at the time of sampling, abundant expression of HIV-1 mRNA in PBMCs predicted accelerated disease progression within the next 2 years. Thus, independently of what may be the rate of HIV replication in other viral reservoirs, such as lymphatic tissue, the amount of HIV mRNA in PBMCs appears to reflect the subsequent development of HIV disease. We have also used the reverse transcriptase-initiated PCR assay to demonstrate a transient response to 3'-azido-3'-deoxythymidine treatment. Determination of HIV-1 mRNA expression in the PBMCs of infected individuals could, therefore, have significant clinical utility as a prognostic indicator and as a means to guiding and monitoring antiviral therapies.