Human Immunodeficiency Virus-1 Impairs IFN-Alpha Production Induced by TLR-7 Agonist in Plasmacytoid Dendritic Cells

Plasmacytoid dendritic cells (pDCs) play an important role in innate immune response against viruses, mainly through interferon-alpha (IFN-alpha) secretion. Impaired IFN-alpha secretion has been observed in patients with acute human immunodeficiency virus type 1 (HIV-1) infection and the reasons for this impairment are still obscure. To know the grounds behind this situation, HIV-1 viral copy numbers similar to those found in primary HIV-1 infection were used to stimulate peripheral blood mononuclear cells (PBMCs) and pDCs in this study. Intracellular IFN-alpha production was seen as early as 2 h in pDCs with TLR-7 agonist (imiquimod) stimulation, but HIV-1 required 48 h to induce secretion of IFN-alpha in supernatants and it was 10 times less compared to imiquimod. Thus, it shows that HIV-1 delays and impairs IFN-alpha production from pDCs. Furthermore, the IFN-alpha inhibitory activity of HIV-1 was checked by stimulating PBMCs and pDCs with imiquimod either simultaneously with HIV-1 or after 2 h pre-exposure to HIV-1. Pre-exposure to HIV-1 resulted in significant reduction in IFN-alpha secretion by pDCs and PBMCs when compared to imiquimod alone. In addition, simultaneous stimulation of these populations with HIV-1 and imiquimod resulted in significant impairment in IFN-alpha production in pDCs but not in PBMCs. HIV-1 not only fails to induce IFN-alpha in adequate quantities but also inhibits IFN-alpha secretary capacity of pDCs. HIV-1 particles were found to bind CD303 receptor on pDC surface probably blocking initiation of cascade leading to IFN-alpha impairment. The understanding of the pathways that lead to this suppression may help in devising the HIV control strategies.