Leukemia inhibitory factor inhibits HIV-1 replication and is upregulated in placentas from nontransmitting women

Leukemia inhibitory factor inhibits HIV-1 replication and is upregulated in placentas from nontransmitting women
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DOI:
10.1172/jci11481
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发表时间:
2001-02-01
影响因子:
15.9
通讯作者:
Andersson, J
Andersson, J
中科院分区:
医学1区
文献类型:
--
作者:
Patterson, BK;Behbahani, H;Andersson, J

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胎盘可能在抑制 HIV-1 垂直传播方面发挥关键作用。在这里,我们证明白血病抑制因子 (LIF) 是一种在胎盘中局部产生的有效内源性 HIV-1 抑制因子。在体外,LIF 对 HIV-1 复制发挥有效的、gp130-LIFR beta 依赖性、HIV 辅助受体独立性抑制作用,IC50 值在 0.1 pg/ml 至 0.7 pg/ml 之间,具体取决于 HIV-1 分离株。 LIF 还抑制离体器官培养物中生长的胎盘和胸腺组织中的 HIV-1。与传播感染的妇女相比,未将 HIV-1 传播给胎儿的 HIV-1 感染妇女的 LIF mRNA 水平和表达 LIF 蛋白的细胞的发生率明显更高,但与未感染母亲的胎盘没有显着差异。这些结局证明了一种内源性 HIV 抑制的新途径,可能被证明是治疗 HIV 感染的有效免疫疗法。
The placenta may play a critical role in inhibiting vertical transmission of HIV-1. Here we demonstrate that leukemia inhibitory factor (LIF) is a potent endogenous HIV-1-suppressive factor produced locally in placentae, In vitro, LIF exerted a potent, gp130-LIFR beta -dependent, HIV coreceptor-independent inhibition of HIV-1 replication with IC50 values between 0.1 pg/ml and 0.7 pg/ml, depending on the HIV-1 isolate. LIF also inhibited HIV-1 in placenta and thymus tissues grown in ex vivo organ culture. The level of LIF mRNA and the incidence of LIF protein-expressing cells were significantly greater ill placentae from HIV-1-infected women who did not transmit HIV-1 to their fetus es compared with women who transmitted the infection, brit they were not significantly different from placentae of uninfected mothers. These Endings demonstrate a novel pathway for endogenous HIV suppression that may prove to be an effective immune therapy for HIV infection.