Background:  Malaria is endemic in countries of Sub-Saharan Africa where HIV-1 infection is also prevalent, pregnant women being the population most at risk of both infections. Epidemiological data and indirect evidence have established a link between placental malaria and an increased risk for HIV-1 mother-to-child transmission (MTCT), by unknown mechanisms.

Methods:  The placenta-derived cell line BeWo and monocyte-derived macrophages (MDM) combinant DBL3g domain, derived from the adhesin PfEMP1 of a Plasmodium falciparum parasite line collected from an infected placenta (DBL3g-732), that binds to chondroitin sulfate A (CSA), was then used to stimulate infected cells. CSA is the major P. falciparum receptor expressed on the surface of human placental cells and is also expressed on MDM. In some experiments, DBL3γ-732 was preincubated with the Fab fragment of a specific monoclonal antibody that inhibits binding to CSA. Tumor necrosis factor-alpha (TNF-a) was measured in the culture supernatants and luciferase activity was quantified

Results:  Addition of DBL3γ-732 to HIV-1-infected BeWo cells led to a dose-dependent increase of HIV-1 replication, reaching as much as 400 times the baseline level. This enhancement was specific as it could be inhibited by the Fab fragment of a monoclonal antibody against DBL3γ-732. In MDM, by contrast, the addition of the same concentrations of DBL3γ-732 induced a strong dose-dependent inhibition of HIV-1 replication. The effect of DBL3γ-732 on HIV-1 replication is most likely mediated by TNF-α as this cytokine was increased by DBL3γ-732 binding to BeWo cells and MDM.

Conclusions:  This study identified for the first time a direct link between a specific Plasmodium antigen and HIV-1 replication. These data underline the importance of efficient malaria prophylaxis together with antiretroviral interventions in areas where HIV-1 and malaria co-circulate. Other strategies based on blocking parasite adhesion to placenta might also be developed in the future to prevent placental malaria and lower the risk of in utero HIV-1 MTCT.