Heterogeneous clearance rates of long-lived lymphocytes infected with HIV:: Intrinsic stability predicts lifelong persistence
Heterogeneous clearance rates of long-lived lymphocytes infected with HIV:: Intrinsic stability predicts lifelong persistence
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DOI：
10.1073/pnas.0736332100
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发表时间：
2003-04-15
影响因子：
11.1
通讯作者：
Wong, JK
中科院分区：
文献类型：
--
作者：
Strain, MC;G端nthard, HF;Wong, JK
病毒复制和潜伏感染的细胞库持续存在于HIV感染患者中，通过有效的抗逆转录病毒治疗达到无法检测的血浆病毒水平。我们利用HIV逆转录酶中可预测的耐药性突变来标记和跟踪在规定的治疗间隔期间感染的细胞，并识别通过持续复制补充的细胞。潜伏性HIV感染细胞亚群的衰变率自成立以来反而随着时间的推移而下降，反映了异质性淋巴细胞活化和清除。残留的低水平复制可以补充细胞库，但是，它不能解释没有检测到病毒血症的患者的清除率延长。在接受强效抗逆转录病毒治疗的患者中，潜伏池具有异质和动态的组成，包括比例逐渐增加的稳定淋巴细胞。仅通过完全抑制病毒复制无法实现根除。
Viral replication and latently infected cellular reservoirs persist in HIV-infected patients achieving undetectable plasma virus levels with potent antiretroviral therapy. We exploited a predictable drug resistance mutation in the HIV reverse transcriptase to label and track cells infected during defined intervals of treatment and to identify cells replenished by ongoing replication. Decay rates of subsets of latently HIV-infected cells paradoxically decreased with time since establishment, reflecting heterogeneous lymphocyte activation and clearance. Residual low-level replication can replenish cellular reservoirs; however, it does not account for prolonged clearance rates in patients without detectable viremia. In patients receiving potent antiretroviral therapy, the latent pool has a heterogeneous and dynamic composition that comprises a progressively increasing proportion of stable lymphocytes. Eradication will not be achieved with-complete inhibition of viral replication alone.