AEGiS-14IAC: Insight into the mechanism of in-utero transmission of AIDS: cytokines expressed by the placenta trigger the replication of HIV-1 in trophoblastic cells.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Insight into the mechanism of in-utero transmission of AIDS: cytokines expressed by the placenta trigger the replication of HIV-1 in trophoblastic cells.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10015)

Vidricaire G, Tremblay MJ
Universite Laval, Ste-Foy, Canada

BACKGROUND: Maternal-infant transmission of HIV-1 is the primary cause of this retrovirus infection in children. The mechanism whereby HIV-1 crosses the placenta to reach the foetus remains poorly understood but the trophoblasts have been proposed to play a role. Given that the placenta is highly regulated via the expression of hormones, cytokines and growth factors, we investigated whether these agents modulate the replication of HIV-1 in trophoblastic cells.

METHODS: Cell lines of trophoblast lineage BeWo, JAR and JEG-3 were inoculated with luciferase expressing single-cycle pseudotyped HIV-1 virions bearing 1) the vesicular stomatitis (VSV-G), 2) HXB-2 (R5) or 3) Ada-M (X4) viral envelope or with the fully infectious virion NL4-3 (X4). Following infection, the cells were treated with increasing doses of cytokines (IL-1 alpha, IL-1 beta, IL-3, IL-4, IL-6, IL-8, IL-10, GM-CSF, CSF-1 or TNF-α) or growth factors (EGF, NGF, TGF). These cells were harvested or co-cultured with LuSIV. Luciferase reporter gene assays were performed.

RESULTS: If no extra-cellular agent was added to the culture media, HIV-1 LTR-mediated reporter gene expression was detected in trophoblastic cells infected with VSV-G pseudotyped HIV-1 virus but not in cells infected with either R5 or X4 pseudotyped HIV-1 virus. However, TNF-α, IL-1 alpha or IL-1 beta lead respectively to a 40, 58, 60 fold increase in LTR activity when added to the trophoblastic infected cells. Moreover, treating cells infected with fully infectious HIV-1 strain NL4-3 (X4) with TNF-α translated into higher viral production.

CONCLUSIONS: The data obtained show for the first time that IL-1 alpha and beta as well as TNF-α, factors expressed by the placenta, trigger the transcriptional activity and replication of HIV-1 in trophoblastic cells. Given that viral production is associated with higher transmission rate, the extra-cellular milieu may contribute to the propagation of HIV-1 across the placenta.

Keywords: AEGIS, HIV-1, Acquired Immunodeficiency Syndrome, Virus Replication, HIV Long Terminal Repeat, Cytokines, HIV Infections, Placenta, Uterus, Interleukin-1, HIV, Trophoblasts, Interleukin-10, Tumor Necrosis Factor, Cell Line, Granulocyte-Macrophage Colony-Stimulating Factor, Greece, Female, Child, Human, Infant, transmission, virology, genetics

020707
A10015