Tumour necrosis factor-α stimulates HIV-1 replication in single-cycle infection of human term placental villi fragments in a time, viral dose and envelope dependent manner
Tumour necrosis factor-α stimulates HIV-1 replication in single-cycle infection of human term placental villi fragments in a time, viral dose and envelope dependent manner
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DOI：
10.1186/1742-4690-3-36
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发表时间：
2006-06-23
期刊：
影响因子：
3.3
通讯作者：
Menu, Elisabeth
中科院分区：
文献类型：
--
作者：
Kfutwah, Anfumbom K. W.;Mary, Jean-Yves;Menu, Elisabeth
背景：胎盘在控制 HIV-1 子宫内母婴传播（MTCT）中发挥着重要作用。胎盘环境中的促炎细胞因子尤其与这种控制有关。因此，我们在体外研究了 TNF-α 对人胎盘组织中 HIV-1 表达的影响。 结果：人胎盘绒毛膜绒毛片段被不同剂量的荧光素酶报告基因 HIV-1 假型（R5、X4-Env 或水泡性口炎病毒蛋白 G (VSVG)）感染。然后在存在或不存在重组人TNF-α的情况下进行组织培养。使用离体成像系统在不同时间点测量细胞裂解物或整个片段的荧光素酶活性。在培养 120 小时后，在 TNF-α 存在的情况下，用 0.2 ng P24 抗原/VSV-G 假型 HIV-1 片段（P = 0.002）感染的胎盘片段中检测到病毒表达显着增加。使用较高剂量的 VSV-G 假型 HIV-1 观察到 TNF-α 病毒表达与时间无关的显着增加。当胎盘碎片感染 R5-Env 假型 HIV-1 时，在培养 168 小时时，测试的 5 个胎盘中有 3 个检测到低水平的 HIV 表达，而 TNF-α 没有统计学上显着的增强。在不存在或存在 TNF-α 的情况下，X4-Env 假型 HIV-1 的感染在任何时间点都不会导致任何可检测到的荧光素酶活性。 结论：胎盘环境中的 TNF-α 会增加 HIV-1 的表达，并可能促进 HIV-1 的 MTCT，特别是在炎症环境中。
Background: The placenta plays an important role in the control of in utero HIV-1 mother-to-child transmission (MTCT). Proinflammatory cytokines in the placental environment are particularly implicated in this control. We thus investigated the effect of TNF-alpha on HIV-1 expression in human placental tissues in vitro.Results: Human placental chorionic villi fragments were infected with varying doses of luciferase reporter HIV-1 pseudotypes with the R5, X4-Env or the vesicular stomatitis virus protein G (VSVG). Histocultures were then performed in the presence or absence of recombinant human TNF-alpha. Luciferase activity was measured at different time points in cell lysates or on whole fragments using ex vivo imaging systems.A significant increase in viral expression was detected in placental fragments infected with 0.2 ng of p24 antigen/ fragment (P = 0.002) of VSV-G pseudotyped HIV-1 in the presence of TNF-alpha seen after 120 hours of culture. A time independent significant increase of viral expression by TNF-alpha was observed with higher doses of VSV-G pseudotyped HIV-1. When placental fragments were infected with R5-Env pseudotyped HIV-1, a low level of HIV expression at 168 hours of culture was detected for 3 of the 5 placentas tested, with no statistically significant enhancement by TNF-alpha. Infection with X4-Env pseudotyped HIV-1 did not lead to any detectable luciferase activity at any time point in the absence or in the presence of TNF-alpha.Conclusion: TNF-alpha in the placental environment increases HIV-1 expression and could facilitate MTCT of HIV-1, particularly in an inflammatory context.