Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo
Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo
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DOI：
10.1128/jvi.73.5.3968-3974.1999
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发表时间：
1999-05-01
影响因子：
5.4
通讯作者：
Margolis, L
中科院分区：
文献类型：
--
作者：
Glushakova, S;Grivel, JC;Margolis, L
nef基因对于与恒河猴中的猿免疫缺陷病毒感染和人类中的人类免疫缺陷病毒1型（HIV-1）感染相关的致病性是重要的。nef参与体内发病的机制尚不清楚，我们通过研究亲本HIV-1毒株NL 4 -3和nef突变体（Delta nefNL 4 -3）的感染，研究了nef对人类淋巴组织中HIV-1复制的贡献。在人扁桃体组织培养中，NL 4 -3的复制水平高于Delta nefNL 4 -3。随着时间的推移，NL 4 -3感染的病毒产量增加与生产性感染细胞数量的增加和CD 4（+）T细胞的更大损失相关。虽然在nef存在下生产性感染T细胞的数量增加，但无论nef基因是否存在，每个感染T细胞的病毒表达和产量水平都是相似的，外源性白细胞介素-2（IL-2）以剂量依赖性方式增加NL 4 -3感染组织中HIV-1的产生。相比之下，Δ nefNL 4 -3的产生仅被IL-2略微增强。因此，Nef可以通过增加生产性感染细胞的数量和通过增加对IL-2刺激的响应性来促进HIV-1在人淋巴组织中的离体复制。
The nef gene is important for the pathogenicity associated with simian immunodeficiency virus infection in rhesus monkeys and with human immunodeficiency virus type 1 (HIV-1) infection in humans. The mechanisms by which nef contributes to pathogenesis in vivo remain unclear,We investigated the contribution of nef to HIV-1 replication in human lymphoid tissue ex vivo by studying infection with parental HIV-I strain NL4-3 and with a nef mutant (Delta nefNL4-3). In human tonsillar histocultures, NL4-3 replicated to higher levels than Delta nefNL4-3 did. Increased, virus production with NL4-3 infection was associated with increased numbers of productively infected cells and greater loss of CD4(+) T cells over time, While the numbers of productively infected T cells were increased in the presence of nef, the levels of viral expression and production per infected T cell were similar whether the nef gene was present or not, Exogenous interleukin-2 (IL-2) increased HIV-1 production in NL4-3-infected tissue in a dose-dependent manner. In contrast, Delta nefNL4-3 production was enhanced only marginally by IL-2, Thus, Nef can facilitate HIV-1 replication in human lymphoid tissue ex vivo by increasing the numbers of productively infected cells and by increasing the responsiveness to IL-2 stimulation.