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

ABSTRACT Apolipoprotein A-I binding protein (AIBP) is a protein involved in regulation of lipid rafts and cholesterol efflux. AIBP has been suggested to function as a protective factor under several sets of pathological conditions associated with increased abundance of lipid rafts, such as atheroscl...

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Autores principales:	Larisa Dubrovsky, Adam Ward, Soo-Ho Choi, Tatiana Pushkarsky, Beda Brichacek, Christophe Vanpouille, Alexei A. Adzhubei, Nigora Mukhamedova, Dmitri Sviridov, Leonid Margolis, Richard B. Jones, Yury I. Miller, Michael Bukrinsky
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	HIV AIBP Nef extracellular vesicles exosomes lipid rafts Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/24158fecd114447eb4e602e7aa4a618f
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spelling	oai:doaj.org-article:24158fecd114447eb4e602e7aa4a618f2021-11-15T15:56:58ZInhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts10.1128/mBio.02956-192150-7511https://doaj.org/article/24158fecd114447eb4e602e7aa4a618f2020-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02956-19https://doaj.org/toc/2150-7511ABSTRACT Apolipoprotein A-I binding protein (AIBP) is a protein involved in regulation of lipid rafts and cholesterol efflux. AIBP has been suggested to function as a protective factor under several sets of pathological conditions associated with increased abundance of lipid rafts, such as atherosclerosis and acute lung injury. Here, we show that exogenously added AIBP reduced the abundance of lipid rafts and inhibited HIV replication in vitro as well as in HIV-infected humanized mice, whereas knockdown of endogenous AIBP increased HIV replication. Endogenous AIBP was much more abundant in activated T cells than in monocyte-derived macrophages (MDMs), and exogenous AIBP was much less effective in T cells than in MDMs. AIBP inhibited virus-cell fusion, specifically targeting cells with lipid rafts mobilized by cell activation or Nef-containing exosomes. MDM-HIV fusion was sensitive to AIBP only in the presence of Nef provided by the virus or exosomes. Peripheral blood mononuclear cells from donors with the HLA-B35 genotype, associated with rapid progression of HIV disease, bound less AIBP than cells from donors with other HLA genotypes and were not protected by AIBP from rapid HIV-1 replication. These results provide the first evidence for the role of Nef exosomes in regulating HIV-cell fusion by modifying lipid rafts and suggest that AIBP is an innate factor that restricts HIV replication by targeting lipid rafts. IMPORTANCE 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-B35 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.Larisa DubrovskyAdam WardSoo-Ho ChoiTatiana PushkarskyBeda BrichacekChristophe VanpouilleAlexei A. AdzhubeiNigora MukhamedovaDmitri SviridovLeonid MargolisRichard B. JonesYury I. MillerMichael BukrinskyAmerican Society for MicrobiologyarticleHIVAIBPNefextracellular vesiclesexosomeslipid raftsMicrobiologyQR1-502ENmBio, Vol 11, Iss 1 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV AIBP Nef extracellular vesicles exosomes lipid rafts Microbiology QR1-502
spellingShingle	HIV AIBP Nef extracellular vesicles exosomes lipid rafts Microbiology QR1-502 Larisa Dubrovsky Adam Ward Soo-Ho Choi Tatiana Pushkarsky Beda Brichacek Christophe Vanpouille Alexei A. Adzhubei Nigora Mukhamedova Dmitri Sviridov Leonid Margolis Richard B. Jones Yury I. Miller Michael Bukrinsky Inhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts
description	ABSTRACT Apolipoprotein A-I binding protein (AIBP) is a protein involved in regulation of lipid rafts and cholesterol efflux. AIBP has been suggested to function as a protective factor under several sets of pathological conditions associated with increased abundance of lipid rafts, such as atherosclerosis and acute lung injury. Here, we show that exogenously added AIBP reduced the abundance of lipid rafts and inhibited HIV replication in vitro as well as in HIV-infected humanized mice, whereas knockdown of endogenous AIBP increased HIV replication. Endogenous AIBP was much more abundant in activated T cells than in monocyte-derived macrophages (MDMs), and exogenous AIBP was much less effective in T cells than in MDMs. AIBP inhibited virus-cell fusion, specifically targeting cells with lipid rafts mobilized by cell activation or Nef-containing exosomes. MDM-HIV fusion was sensitive to AIBP only in the presence of Nef provided by the virus or exosomes. Peripheral blood mononuclear cells from donors with the HLA-B35 genotype, associated with rapid progression of HIV disease, bound less AIBP than cells from donors with other HLA genotypes and were not protected by AIBP from rapid HIV-1 replication. These results provide the first evidence for the role of Nef exosomes in regulating HIV-cell fusion by modifying lipid rafts and suggest that AIBP is an innate factor that restricts HIV replication by targeting lipid rafts. IMPORTANCE 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-B35 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.
format	article
author	Larisa Dubrovsky Adam Ward Soo-Ho Choi Tatiana Pushkarsky Beda Brichacek Christophe Vanpouille Alexei A. Adzhubei Nigora Mukhamedova Dmitri Sviridov Leonid Margolis Richard B. Jones Yury I. Miller Michael Bukrinsky
author_facet	Larisa Dubrovsky Adam Ward Soo-Ho Choi Tatiana Pushkarsky Beda Brichacek Christophe Vanpouille Alexei A. Adzhubei Nigora Mukhamedova Dmitri Sviridov Leonid Margolis Richard B. Jones Yury I. Miller Michael Bukrinsky
author_sort	Larisa Dubrovsky
title	Inhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts
title_short	Inhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts
title_full	Inhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts
title_fullStr	Inhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts
title_full_unstemmed	Inhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts
title_sort	inhibition of hiv replication by apolipoprotein a-i binding protein targeting the lipid rafts
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/24158fecd114447eb4e602e7aa4a618f
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Inhibition of HIV Replication by Apolipoprotein A-I Binding Protein Targeting the Lipid Rafts

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