Leishmania Infantum Promastigotes Reduce Entry of HIV-1 into Macrophages Through a Lipophosphoglycan-mediated Disruption of Lipid Rafts

Visceral leishmaniasis is now recognized as an opportunistic disease in patients infected with human immunodeficiency virus type 1 (HIV-1). We report here that Leishmania infantum promastigotes enhance HIV-1 replication in monocyte-derived macrophages (MDMs) at late time points in the virus growth curve but also that, surprisingly, a reduction in HIV-1 production is seen during the initial days after infection. This early effect is caused by a Leishmania-mediated inhibition of virus entry into MDMs through the action of lipophosphoglycan (LPG), the major promastigote surface glycolipid. The impact of LPG in the observed phenomenon was confirmed using LPG-defective lpg1-/- knockout mutant promastigotes. Our results suggest that the LPG-mediated effect results from the disruption of lipid rafts. Altogether, these findings suggest that the presence of Leishmania within the same cellular microenvironment leads to 2 opposite, time-dependent effects on HIV-1 replication. Leishmania and HIV-1 can thus establish complex interactions in their common natural host cells.