Kfutwah Anfumbom K W, Mary Jean-Yves, Nicola Marie-Anne, Blaise-Boisseau Sandra, Barré-Sinoussi Françoise, Ayouba Ahidjo, Menu Elisabeth
Laboratory of Virology, Centre Pasteur du Cameroun, Yaoundé, Cameroon.
Retrovirology. 2006 Jun 23;3:36. doi: 10.1186/1742-4690-3-36.
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.
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 (VSV-G). 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.
TNF-alpha in the placental environment increases HIV-1 expression and could facilitate MTCT of HIV-1, particularly in an inflammatory context.
胎盘在控制子宫内HIV-1母婴传播（MTCT）中起重要作用。胎盘环境中的促炎细胞因子尤其与此控制有关。因此，我们在体外研究了肿瘤坏死因子-α（TNF-α）对人胎盘组织中HIV-1表达的影响。
用人胎盘绒毛膜绒毛片段感染不同剂量的带有R5、X4包膜或水泡性口炎病毒蛋白G（VSV-G）的荧光素酶报告HIV-1假型。然后在有或无重组人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中的荧光素酶活性。在培养120小时后，在存在TNF-α的情况下，用0.2 ng p24抗原/片段的VSV-G假型HIV-1感染的胎盘片段中检测到病毒表达显著增加（P = 0.002）。对于更高剂量的VSV-G假型HIV-1，观察到TNF-α对病毒表达有与时间无关的显著增加。当胎盘片段用R5包膜假型HIV-1感染时，在测试的5个胎盘中有3个在培养168小时时检测到低水平的HIV表达，TNF-α没有统计学上显著的增强作用。用X4包膜假型HIV-1感染在不存在或存在TNF-α的任何时间点均未导致任何可检测到的荧光素酶活性。
胎盘环境中的TNF-α增加HIV-1表达，并可能促进HIV-1的母婴传播，特别是在炎症背景下。
