CD4+ T-cell recovery with suppressive ART-induced rapid sequence evolution in hepatitis C virus envelope but not NS3.
CD4+ T-cell recovery with suppressive ART-induced rapid sequence evolution in hepatitis C virus envelope but not NS3.
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DOI：
10.1097/qad.0000000000000997
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发表时间：
2016-03-13
期刊：
影响因子：
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通讯作者：
Wang GP
中科院分区：
文献类型：
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作者：
Liu L;Nardo D;Li E;Wang GP
人类免疫缺陷病毒（HIV）感染导致的CD 4 + T细胞耗竭导致抗丙型肝炎病毒（HCV）包膜中和抗体（nAb）反应的全球下降，这可能在加速肝纤维化中发挥作用。在抗逆转录病毒治疗（ART）期间，抗HCV nAb滴度增加，但其对HCV的影响仍知之甚少。本研究的目的是确定ART对HCV长期演变的影响。我们研究了HIV/HCV共感染受试者中抗逆转录病毒治疗诱导的CD 4 + T细胞恢复的HCV准种结构和长期进化，并与延迟抗逆转录病毒治疗导致的CD 4 + T细胞耗竭的受试者进行了比较。我们应用单变异测序（SVS）方法构建了真实的病毒准种，并比较了HCV包膜（体液免疫应答的主要靶点）和NS 3中的序列进化，细胞免疫的目标，在两个群体之间。SVS方法纠正了已知的偏差，使病毒变异体的比例发生偏差，揭示了真实的HCV准种结构。我们观察到ART诱导的CD 4 + T细胞恢复受试者中HCV包膜序列演变率高于延迟ART导致的CD 4 + T细胞耗竭受试者（P=0.03）。NS 3的进化率显著低于包膜的进化率（P<0.01），两组之间没有观察到显著差异。ART诱导的CD 4 + T细胞恢复导致HCV包膜中的快速序列进化，但不是NS 3。这些结果表明，抑制性ART预防性地增强HCV特异性体液应答而不是细胞应答，导致HCV包膜而不是NS 3中的快速序列进化。
CD4+ T-cell depletion from human immunodeficiency virus (HIV) infection leads to a global decline in anti-hepatitis C virus (HCV) envelope neutralizing antibody (nAb) response, which may play a role in accelerating liver fibrosis. An increase in anti-HCV nAb titers has been reported during antiretroviral therapy (ART) but its impact on HCV remains poorly understood. The objective of this study is to determine the effects of ART on long-term HCV evolution. We examined HCV quasispecies structure and long-term evolution in HIV/HCV co-infected subjects with ART-induced CD4+ T-cell recovery, and compared to subjects with CD4+ T-cell depletion from delayed ART. We applied a single-variant sequencing (SVS) method to construct authentic viral quasispecies and compared sequence evolution in HCV envelope, the primary target for humoral immune responses, and NS3, a target for cellular immunity, between the two cohorts. The SVS method corrected biases known to skew the proportions of viral variants, revealing authentic HCV quasispeices structures. We observed higher rates of HCV envelope sequence evolution in subjects with ART-induced CD4+ T-cell recovery, compared to subjects with CD4+ T-cell depletion from delayed ART (P=0.03). Evolutionary rates for NS3 were considerably lower than the rates for envelope (P<0.01), with no significant difference observed between the two groups. ART-induced CD4+ T-cell recovery results in rapid sequence evolution in HCV envelope, but not in NS3. These results suggest that suppressive ART disproportionally enhances HCV-specific humoral responses more than cellular responses, resulting in rapid sequence evolution in HCV envelope but not NS3.