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首页> 外文期刊>AIDS Research and Human Retroviruses >Increasing CTL targeting of conserved sequences during early HIV-1 infection is correlated to decreasing viremia.
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Increasing CTL targeting of conserved sequences during early HIV-1 infection is correlated to decreasing viremia.

机译：在早期HIV-1感染期间增加保守序列的CTL靶向性与降低病毒血症相关。

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摘要

Early HIV-1 infection is marked by rapid evolution of both CD8(+) T lymphocyte (CTL) epitope targeting and viral sequences, while chronic infection demonstrates relative stability of these parameters. To examine the interactions of changing CTL targeting and viremia in early infection, we assessed CTL targeting and viremia levels in persons during early HIV-1 infection (estimated 15-271 days post-infection) who were placed on effective antiretroviral therapy. Pre-therapy, CTL targeting of viral proteins varied between persons depending on time after infection. Across individuals, increasing time after infection was associated with increasing Gag and Pol targeting, suggesting increasing targeting of conserved sequences. The intensity of Gag targeting correlated to lower viremia levels, while Env targeting correlated to higher viremia levels during early infection. This suggested that shifted targeting towards more conserved sequences is involved with the drop of viremia during early infection, consistent with prior observations of correlation between Gag targeting and lower viremia during chronic infection. After suppressive antiretroviral therapy, CTL targeting was generally static, indicating that HIV-1 replication and evolution drives the evolution of CTL targeting in early infection. Overall, these data suggest that early CTL targeting is directed towards more variable epitopes, causing escape and re-targeting until more conserved epitopes are recognized stably in chronic infection. Circumventing this natural history by pre-targeting CTL against more conserved epitopes with a vaccine could minimize the initial period of viral escape and immune damage during acute infection, improving long-term containment of HIV-1.
机译：早期HIV-1感染的特征在于CD8（+）T淋巴细胞（CTL）表位靶向和病毒序列的快速进化，而慢性感染证明了这些参数的相对稳定性。为了检查早期感染中CTL靶向和病毒血症变化的相互作用，我们评估了接受有效抗逆转录病毒治疗的早期HIV-1感染（估计感染后15-271天）患者的CTL靶向和病毒血症水平。治疗前，根据感染后的时间，人间对病毒蛋白的CTL靶点有所不同。在整个个体中，感染后时间的增加与Gag和Pol靶向作用的增加有关，提示对保守序列的靶向作用的增加。 Gag靶向的强度与较低的病毒血症水平相关，而Env靶向与早期感染期间的较高病毒血症水平相关。这表明在早期感染过程中，靶标向更保守序列的转移与病毒血症的下降有关，这与先前在慢性感染期间Gag靶标与较低病毒血症之间相关性的观察结果一致。抑制性抗逆转录病毒疗法后，CTL靶向通常是静态的，表明HIV-1复制和进化驱动了早期感染中CTL靶向的进化。总体而言，这些数据表明，早期CTL靶向针对更多可变的表位，导致逃逸和重新靶向，直到在慢性感染中稳定地识别出更多保守的表位。通过用疫苗预先将CTL靶向更保守的表位来规避这种自然历史，可以最大程度地减少急性感染期间病毒逃逸和免疫损伤的初始阶段，从而改善对HIV-1的长期控制。

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