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

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Abstract

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-LIFRβ–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 in placentae from HIV-1–infected women who did not transmit HIV-1 to their fetuses compared with women who transmitted the infection, but they were not significantly different from placentae of uninfected mothers. These findings demonstrate a novel pathway for endogenous HIV suppression that may prove to be an effective immune therapy for HIV infection.

Authors

Bruce K. Patterson, Homira Behbahani, William J. Kabat, Yvonne Sullivan, Maurice R.G. O’Gorman, Alan Landay, Zareefa Flener, Nadia Khan, Ram Yogev, Jan Andersson