HIV-R viral escape in infancy followed by emergence of a variant-specific CTL response
HIV-R viral escape in infancy followed by emergence of a variant-specific CTL response
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DOI：
10.4049/jimmunol.174.12.7524
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发表时间：
2005-06-15
影响因子：
4.4
通讯作者：
Goulder, PJR
中科院分区：
文献类型：
--
作者：
Feeney, ME;Tang, YH;Goulder, PJR
CTL反应的突变逃逸是HIV-1感染成人中病毒多样化的主要驱动力，但婴儿期的逃逸此前尚未被描述过。我们研究了围产期感染儿童对表位 (B57-TW10) 的免疫反应，该表位是表达 HLA-B57 的成人急性 HIV-1 感染早期的目标，并在这种选择压力下迅速突变。病毒测序揭示了 B57 和 B5801 阳性儿童中 TW10 普遍存在逃逸突变。 B57 阴性母亲所生的 B57 阳性儿童在围产期感染后，TW10 和其他 B57 限制性表位的突变很早就出现。令人惊讶的是，大多数 B57/5801 阳性儿童对 TW10 逃逸变体表现出强烈的反应，而对野生型表位的识别较弱或根本不识别。这些数据表明，儿童即使在生命的最初几年，也能够产生足够效力的功能性免疫反应来驱动免疫逃逸。此外，我们的数据表明，免疫逃逸的后果在婴儿期可能有所不同，因为大多数儿童在逃逸后会产生强烈的变异特异性免疫反应，这在成人中很少见。总而言之，这些发现表明，儿童正在发育的免疫系统在应对不断演变的慢性病毒感染时可能表现出更大的可塑性。
Mutational escape from the CTL response represents a major driving force for viral diversification in HIV-1-infected adults, but escape during infancy has not been described previously. We studied the immune response of perinatally infected children to an epitope (B57-TW10) that is targeted early during acute HIV-1 infection in adults expressing HLA-B57 and rapidly mutates under this selection pressure. Viral sequencing revealed the universal presence of escape mutations within TW10 among B57- and B5801-positive children. Mutations in TW10 and other B57-restricted epitopes arose early following perinatal infection of B57-positive children born to B57-negative mothers. Surprisingly, the majority of B57/5801-positive children exhibited a robust response to the TW10 escape variant while recognizing the wild-type epitope weakly or not at all. These data demonstrate that children, even during the first years of life, are able to mount functional immune responses of sufficient potency to drive immune escape. Moreover, our data suggest that the consequences of immune escape may differ during infancy because most children mount a strong variant-specific immune response following escape, which is rarely seen in adults. Taken together, these findings indicate that the developing immune system of children may exhibit greater plasticity in responding to a continually evolving chronic viral infection.