Inhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts

Author:

Dubrovsky Larisa1,Ward Adam1,Choi Soo-Ho2,Pushkarsky Tatiana1,Brichacek Beda1,Vanpouille Christophe3,Adzhubei Alexei A.14,Mukhamedova Nigora5,Sviridov Dmitri5,Margolis Leonid3,Jones Richard B.1,Miller Yury I.2,Bukrinsky Michael1

Affiliation:

1. The George Washington University School of Medicine and Health Sciences, Washington, DC, USA

2. University of California San Diego, La Jolla, California, USA

3. Eunice Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA

4. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia

5. Baker Heart and Diabetes Research Institute, Melbourne, Victoria, Australia

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.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

American Heart Association

HHS | NIH | National Institute of Neurological Disorders and Stroke

HHS | NIH | National Heart, Lung, and Blood Institute

Российский Фонд Фундаментальных Исследований (РФФИ)

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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