Bailey Justin R, Sedaghat Ahmad R, Kieffer Tara, Brennan Timothy, Lee Patricia K, Wind-Rotolo Megan, Haggerty Christine M, Kamireddi Ashrit R, Liu Yi, Lee Jessica, Persaud Deborah, Gallant Joel E, Cofrancesco Joseph, Quinn Thomas C, Wilke Claus O, Ray Stuart C, Siliciano Janet D, Nettles Richard E, Siliciano Robert F
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
J Virol. 2006 Jul;80(13):6441-57. doi: 10.1128/JVI.00591-06.
Antiretroviral therapy can reduce human immunodeficiency virus type 1 (HIV-1) viremia to below the detection limit of ultrasensitive clinical assays (50 copies of HIV-1 RNA/ml). However, latent HIV-1 persists in resting CD4+ T cells, and low residual levels of free virus are found in the plasma. Limited characterization of this residual viremia has been done because of the low number of virions per sample. Using intensive sampling, we analyzed residual viremia and compared these viruses to latent proviruses in resting CD4+ T cells in peripheral blood. For each patient, we found some viruses in the plasma that were identical to viruses in resting CD4+ T cells by pol gene sequencing. However, in a majority of patients, the most common viruses in the plasma were rarely found in resting CD4+ T cells even when the resting cell compartment was analyzed with assays that detect replication-competent viruses. Despite the large diversity of pol sequences in resting CD4+ T cells, the residual viremia was dominated by a homogeneous population of viruses with identical pol sequences. In the most extensively studied case, a predominant plasma sequence was also found in analysis of the env gene, and linkage by long-distance reverse transcriptase PCR established that these predominant plasma sequences represented a single predominant plasma virus clone. The predominant plasma clones were released for months to years without evident sequence change. Thus, in some patients on antiretroviral therapy, the major mechanism for residual viremia involves prolonged production of a small number of viral clones without evident evolution, possibly by cells other than circulating CD4+ T cells. The sequences have been deposited in GenBank. The accession numbers are DQ 391282 to DQ 391351 (for env) and DQ 391352 to DQ 392955 (for RT).
抗逆转录病毒疗法可将1型人类免疫缺陷病毒（HIV-1）病毒血症降低至超敏临床检测法的检测限以下（HIV-1 RNA 50拷贝/毫升）。然而，潜伏的HIV-1持续存在于静息CD4+ T细胞中，并且在血浆中可检测到低残留水平的游离病毒。由于每个样本中的病毒粒子数量较少，对这种残留病毒血症的特征描述有限。我们通过密集采样分析了残留病毒血症，并将这些病毒与外周血静息CD4+ T细胞中的潜伏前病毒进行了比较。对每位患者而言，通过pol基因测序，我们在血浆中发现了一些与静息CD4+ T细胞中的病毒相同的病毒。然而，在大多数患者中，即使使用能够检测有复制能力病毒的检测方法分析静息细胞区室，血浆中最常见的病毒在静息CD4+ T细胞中也很少被发现。尽管静息CD4+ T细胞中的pol序列具有很大的多样性，但残留病毒血症主要由具有相同pol序列的同源病毒群体主导。在研究最为深入的病例中，在env基因分析中也发现了一种占主导地位的血浆序列，通过长距离逆转录酶PCR进行的连锁分析确定，这些占主导地位的血浆序列代表单一的占主导地位的血浆病毒克隆。这些占主导地位的血浆克隆在数月至数年的时间里持续释放，且序列没有明显变化。因此，在一些接受抗逆转录病毒治疗的患者中，残留病毒血症的主要机制涉及少数病毒克隆的长期产生且无明显进化，可能是由循环CD4+ T细胞以外的细胞产生的。这些序列已存入GenBank。登录号为DQ 391282至DQ 391351（用于env）和DQ 391352至DQ 392955（用于RT）。
