Inhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts
Larisa Dubrovsky, Adam R. Ward, Soo‐Ho Choi, Tatiana Pushkarsky, Beda Břicháček, Christophe Vanpouille, Alexei A. Adzhubei, Nigora Mukhamedova, Dmitri Sviridov, Leonid Margolis, R. Brad Jones, Yury I. Miller, Michael Bukrinsky
Abstract
Apolipoprotein A-I binding protein (AIBP) is a recently identified innate anti-inflammatory factor. Here, we show that AIBP inhibited HIV replication by targeting lipid rafts and reducing virus-cell fusion. Importantly, AIBP selectively reduced levels of rafts on cells stimulated by an inflammatory stimulus or treated with extracellular vesicles containing HIV-1 protein Nef without affecting rafts on nonactivated cells. Accordingly, fusion of monocyte-derived macrophages with HIV was sensitive to AIBP only in the presence of Nef. Silencing of endogenous AIBP significantly upregulated HIV-1 replication. Interestingly, HIV-1 replication in cells from donors with the HLA-B*35 genotype, associated with rapid progression of HIV disease, was not inhibited by AIBP. These results suggest that AIBP is an innate anti-HIV factor that targets virus-cell fusion.