INDUCTION OF CD4 AND SUSCEPTIBILITY TO HIV-1 INFECTION IN HUMAN CD8+ LYMPHOCYTES-T BY HUMAN HERPESVIRUS-6
INDUCTION OF CD4 AND SUSCEPTIBILITY TO HIV-1 INFECTION IN HUMAN CD8+ LYMPHOCYTES-T BY HUMAN HERPESVIRUS-6
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DOI：
10.1038/349533a0
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发表时间：
1991-02-07
期刊：
影响因子：
64.8
通讯作者：
GALLO, RC
中科院分区：
文献类型：
--
作者：
LUSSO, P;DEMARIA, A;GALLO, RC
在胸腺内T细胞个体发生期间，有功能的CD 3 + CD 4 + CD 8-和CD 3 + CD 4-CD 8 + T淋巴细胞在短暂获得双阳性CD 4 + CD 8+表型1-3后从未成熟的CD 4-CD 8-胸腺细胞发育而来。 CD 4 + CD 8-和CD 4-CD 8 + T细胞之间的分配通常被认为是不可逆的，尽管已经鉴定了小百分比的共表达CD 4和CD 8分子的循环CD 3 + T淋巴细胞4。 有人提出，在CD 8 + T细胞中，CD 4基因可能被甲基化，因此受到高度抑制5，而在CD 4 + T细胞中，CD 8基因未被甲基化6，它们的转录可以被生理刺激物如白细胞介素-4诱导（参考文献7）。 在这里，我们证明了人类疱疹病毒6型（HHV-6）（参考文献8），一种被认为是艾滋病潜在辅助因子的病毒（参考文献9），在人类肿瘤T细胞系中显著上调了CD 4-人类免疫缺陷病毒1型（HIV-1）受体（参考文献10-12）的表达。 更重要的是，HHV-6诱导正常成熟CDE 8 + T淋巴细胞中CD 4信使RNA和蛋白质的从头表达，使其易于感染HIV-1。 这些结果表明，人CD 3 + CD 4-CD 8 + T淋巴细胞可以重新获得CD 4在胸腺后的生活和阐明一种新的机制-受体调节-通过HHV-6可能与HIV-1的积极相互作用在合并感染的患者。
DURING intrathymic T-cell ontogenesis, functionally competent CD3+CD4+CD8- and CD3+CD4-CD8+ T lymphocytes develop from immature CD4-CD8- thymocytes after transiently acquiring a double-positive CD4+CD8+ phenotype 1-3. The partition between CD4+CD8- and CD4-CD8+ T cells is generally considered to be irreversible, although a small percentage of circulating CD3+ T lymphocytes coexpressing CD4 and CD8 molecules has been identified 4. It has been suggested that in CD8+ T cells the CD4 genes may be methylated and thus highly repressed 5, whereas in CD4+ T cells the CD8 genes are unmethylated 6 and their transcription can be induced by physiological stimuli such as interleukin-4 (ref. 7). Here, we demonstrate that infection with human herpesvirus 6 (HHV-6) (ref. 8), a virus proposed as a potential cofactor in AIDS (ref. 9), dramatically upregulates the expression of CD4-the receptor for human immunodeficiency virus type-1 (HIV-1) (refs 10-12)-in a human neoplastic T-cell line. More importantly, HHV-6 induces de novo expression of CD4 messenger RNA and protein in normal mature CDE8+ T lymphocytes, rendering them susceptible to infection with HIV-1. These findings demonstrate that human CD3+CD4-CD8+ T lymphocytes can reacquire CD4 in the post-thymic life and elucidate a novel mechanism-receptor regulation-through which HHV-6 may positively interact with HIV-1 in coinfected patients.