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人类免疫缺陷病毒 1 型在围产期感染儿童胸腺内的有限进化。

Limited evolution of human immunodeficiency virus type 1 in the thymus of a perinatally infected child.

机构信息

Department of Pediatrics, Emory University School of Medicine, Atlanta Georgia, USA.

出版信息

Clin Infect Dis. 2010 Mar 1;50(5):726-32. doi: 10.1086/650453.

DOI:10.1086/650453
PMID:20100091
Abstract

BACKGROUND

Involvement of the thymus during human immunodeficiency virus (HIV) infection may impair production of naive lymphocytes leading to more rapid depletion, but the characteristics of primary strains in the thymus are not well studied because of the unavailability of tissue in living individuals.

METHODS

We studied the characteristics of HIV type 1 (HIV-1) in a 5-year old perinatally infected child with thymitis and compared the genomic sequences of the HIV-1 C2-V5 region of the env gene in the thymic tissue and peripheral blood.

RESULTS

The thymus harbored predominantly viral sequences close to the founder HIV-1 variant that circulated in the blood at 2 and 3 months of age, whereas the peripheral blood virus at 5 years of age had evolved extensively. Viral sequences from circulating CD8(+) T cells at 5 years of age phylogenetically clustered with those from the thymic tissue.

CONCLUSIONS

These results indicate the existence of a distinct thymic viral reservoir and suggest that circulating CD8(+) T cells were infected in the thymus, presumably at the CD4(+)CD8(+) thymocyte stage. They also demonstrate that not all thymic HIV infections will necessarily lead to severe thymic dysfunction. The characteristics of the virus strain seeding the thymus may dictate the rate of disease progression.

摘要

背景

人类免疫缺陷病毒(HIV)感染期间的胸腺参与可能会损害幼稚淋巴细胞的产生,导致更快的耗竭,但由于无法获得活体组织,胸腺内原发性毒株的特征尚未得到很好的研究。

方法

我们研究了一名 5 岁经胎盘感染的儿童胸腺炎中 HIV-1 的特征,并比较了胸腺组织和外周血中 HIV-1 C2-V5 区 env 基因的 HIV-1 基因组序列。

结果

胸腺内主要存在与 2 个月和 3 个月龄时血液中循环的原始 HIV-1 变体接近的病毒序列,而 5 岁时的外周血病毒则广泛进化。5 岁时循环 CD8+T 细胞中的病毒序列与胸腺组织中的病毒序列在系统发育上聚类。

结论

这些结果表明存在独特的胸腺病毒库,并提示循环 CD8+T 细胞是在胸腺内感染的,推测是在 CD4+CD8+胸腺细胞阶段。它们还表明,并非所有胸腺内的 HIV 感染都会导致严重的胸腺功能障碍。播种胸腺的病毒株的特征可能决定疾病进展的速度。

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