Soriano-Sarabia Natalia, Bateson Rosalie E, Dahl Noelle P, Crooks Amanda M, Kuruc JoAnn D, Margolis David M, Archin Nancie M
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
J Virol. 2014 Dec;88(24):14070-7. doi: 10.1128/JVI.01900-14. Epub 2014 Sep 24.
Central memory (TCM) CD4(+) T cells are the principal reservoir of latent HIV-1 infection that persists despite durable, successful antiretroviral therapy (ART). In a study that measured HIV DNA in 17 patients and replication-competent HIV in 4 patients, pools of resting and activated transitional memory (T(TM)) CD4(+) T cells were found to be a reservoir for HIV infection. As defective viruses account for the majority of integrated HIV DNA and do not reflect the actual frequency of latent, replication-competent proviral infection, we assessed the specific contribution of resting T(TM) cells to latent HIV infection. We measured the frequency of replication-competent HIV in purified resting memory cell subpopulations by a limiting-dilution, quantitative viral outgrowth assay (QVOA). HIV was routinely detected within the resting central memory compartment but was infrequently detected within the resting T(TM) compartment. These observations suggest that prolonged ART may limit persistent latent infection in the T(TM) compartment. Our results confirm the importance of latent infection within the TCM compartment and again focus attention on these cells as the most important latent viral reservoir. While proliferation may drive expansion of detectable viral genomes in cells, the frequency of replication-competent HIV must be carefully assessed. Latent infection appears to wane within the transitional memory compartment in patients who have sustained successful viral suppression via ART or were treated very early in infection.
Antiretroviral therapy (ART) has led to a significant decrease in morbidity and mortality among HIV-infected patients. However, HIV integrates into the genome of CD4(+) T cells, generating pools of long-lived cells that are reservoirs of latent HIV. Two main subsets of CD4(+) T cells, central memory and transitional memory cells, were reported to be major reservoirs of HIV infection. However, this study primarily measured the HIV DNA content, which also includes defective proviruses that would not be able to replicate and initiate new rounds of infection. By analyzing the replication-competent virus in both cell subsets, we showed that transitional memory cells may not be a durable reservoir in patients on successful ART.
中枢记忆（TCM）CD4(+) T细胞是潜伏性HIV-1感染的主要储存库，尽管抗逆转录病毒疗法（ART）持久且成功，但这种感染仍会持续存在。在一项对17名患者的HIV DNA以及4名患者中具有复制能力的HIV进行检测的研究中，静息和活化的过渡记忆（T(TM)）CD4(+) T细胞库被发现是HIV感染的一个储存库。由于缺陷病毒占整合HIV DNA的大多数，且不能反映潜伏的、具有复制能力的前病毒感染的实际频率，我们评估了静息T(TM)细胞对潜伏性HIV感染的具体贡献。我们通过有限稀释定量病毒增殖试验（QVOA）测量了纯化的静息记忆细胞亚群中具有复制能力的HIV的频率。HIV通常在静息中枢记忆区被检测到，但在静息T(TM)区很少被检测到。这些观察结果表明，长期ART可能会限制T(TM)区的持续性潜伏感染。我们的结果证实了TCM区潜伏感染的重要性，并再次将注意力集中在这些细胞上，认为它们是最重要的潜伏病毒储存库。虽然增殖可能会推动细胞中可检测到的病毒基因组的扩增，但必须仔细评估具有复制能力的HIV的频率。在通过ART实现持续成功病毒抑制或在感染早期接受治疗的患者中，潜伏感染似乎在过渡记忆区有所减弱。
抗逆转录病毒疗法（ART）已导致HIV感染患者的发病率和死亡率显著下降。然而，HIV会整合到CD4(+) T细胞的基因组中，产生长寿细胞库，这些细胞是潜伏性HIV的储存库。据报道，CD4(+) T细胞的两个主要亚群，即中枢记忆细胞和过渡记忆细胞，是HIV感染的主要储存库。然而，这项研究主要测量的是HIV DNA含量，其中还包括无法复制并引发新一轮感染的缺陷前病毒。通过分析这两个细胞亚群中具有复制能力的病毒，我们表明，对于接受成功ART治疗的患者，过渡记忆细胞可能不是一个持久的储存库。
