Requirement for the second coding exon of Tat in the optimal replication of macrophage-tropic HIV-1

Requirement for the second coding exon of Tat in the optimal replication of macrophage-tropic HIV-1
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DOI:
10.1159/000073531
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发表时间:
2003-01-01
影响因子:
11
通讯作者:
Jeang, KT
Jeang, KT
中科院分区:
医学1区
文献类型:
--
作者:
Neuveut, C;Scoggins, RM;Jeang, KT

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HIV-1达特是病毒复制所必需的,并且是病毒基因表达的有效反式激活因子。有证据表明,达特也影响病毒的感染性和细胞病变。在这里,我们发现,第二个编码外显子的达特贡献了一个新的功能的复制/感染性的巨噬细胞嗜性HIV-1。我们表明,嗜巨噬细胞的HIV-1,表达全长两个外显子形式的达特复制更好地在单核细胞衍生的巨噬细胞(MDM)比其他同基因病毒只表达一个外显子形式的达特。类似地,在两种不同的人细胞/组织重建的SCID小鼠模型中,表达HIV-1的双外显子达特的复制也优于表达HIV-1的单外显子达特。版权所有(C)2003国家科学理事会,中华民国和S. Karger AG,巴塞尔。
HIV-1 Tat is essential for virus replication and is a potent transactivator of viral gene expression. Evidence suggests that Tat also influences virus infectivity and cytopathicity. Here, we find that the second coding exon of Tat contributes a novel function for the replication/infectivity of macrophage-tropic HIV-1. We show that macrophage-tropic HIV-1 which expresses the full-length two-exon form of Tat replicates better in monocyte-derived macrophages (MDM) than an otherwise isogenic virus which expresses only the one-exon form of Tat. Similarly, two-exon Tat expressing HIV-1 also replicates better than one-exon Tat expressing HIV-1 in two different models of human cells/tissue reconstituted SCID mice. Copyright (C) 2003 National Science Council, ROC and S. Karger AG, Basel.