CD4<sup>+</sup> T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy

ABSTRACT Therapeutic strategies that provide effective and broad‐spectrum neutralization against HIV-1 infection are highly desirable. Here, we investigate the potential of nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP) to neutralize a broad range of HIV-1 strains. TNP displayed outs...

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Autores principales:	Gang Zhang, Grant R. Campbell, Qiangzhe Zhang, Erin Maule, Jonathan Hanna, Weiwei Gao, Liangfang Zhang, Stephen A. Spector
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	HIV nanoparticle autophagy neutralization CD4+ T cell macrophage Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/bcd1ffecf9ad42c095dd956fce43381e
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spelling	oai:doaj.org-article:bcd1ffecf9ad42c095dd956fce43381e2021-11-15T16:19:08ZCD4<sup>+</sup> T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy10.1128/mBio.00903-202150-7511https://doaj.org/article/bcd1ffecf9ad42c095dd956fce43381e2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00903-20https://doaj.org/toc/2150-7511ABSTRACT Therapeutic strategies that provide effective and broad‐spectrum neutralization against HIV-1 infection are highly desirable. Here, we investigate the potential of nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP) to neutralize a broad range of HIV-1 strains. TNP displayed outstanding neutralizing breadth and potency; they neutralized all 125 HIV-1-pseudotyped viruses tested, including global subtypes/recombinant forms, and transmitted/founder viruses, with a geometric mean 80% inhibitory concentration (IC80) of 819 μg ml−1 (range, 72 to 8,570 μg ml−1). TNP also selectively bound to and induced autophagy in HIV-1-infected CD4+ T cells and macrophages, while having no effect on uninfected cells. This TNP-mediated autophagy inhibited viral release and reduced cell-associated HIV-1 in a dose- and phospholipase D1-dependent manner. Genetic or pharmacological inhibition of autophagy ablated this effect. Thus, we can use TNP as therapeutic agents to neutralize cell-free HIV-1 and to target HIV-1 gp120-expressing cells to decrease the HIV-1 reservoir. IMPORTANCE HIV-1 is a major global health challenge. The development of an effective vaccine and/or a therapeutic cure is a top priority. The creation of vaccines that focus an antibody response toward a particular epitope of a protein has shown promise, but the genetic diversity of HIV-1 hinders this progress. Here we developed an approach using nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP). Not only do TNP effectively neutralize all strains of HIV-1, but they also selectively bind to infected cells and decrease the release of HIV-1 particles through an autophagy-dependent mechanism with no drug-induced off-target or cytotoxic effects on bystander cells.Gang ZhangGrant R. CampbellQiangzhe ZhangErin MauleJonathan HannaWeiwei GaoLiangfang ZhangStephen A. SpectorAmerican Society for MicrobiologyarticleHIVnanoparticleautophagyneutralizationCD4+ T cellmacrophageMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV nanoparticle autophagy neutralization CD4+ T cell macrophage Microbiology QR1-502
spellingShingle	HIV nanoparticle autophagy neutralization CD4+ T cell macrophage Microbiology QR1-502 Gang Zhang Grant R. Campbell Qiangzhe Zhang Erin Maule Jonathan Hanna Weiwei Gao Liangfang Zhang Stephen A. Spector CD4<sup>+</sup> T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy
description	ABSTRACT Therapeutic strategies that provide effective and broad‐spectrum neutralization against HIV-1 infection are highly desirable. Here, we investigate the potential of nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP) to neutralize a broad range of HIV-1 strains. TNP displayed outstanding neutralizing breadth and potency; they neutralized all 125 HIV-1-pseudotyped viruses tested, including global subtypes/recombinant forms, and transmitted/founder viruses, with a geometric mean 80% inhibitory concentration (IC80) of 819 μg ml−1 (range, 72 to 8,570 μg ml−1). TNP also selectively bound to and induced autophagy in HIV-1-infected CD4+ T cells and macrophages, while having no effect on uninfected cells. This TNP-mediated autophagy inhibited viral release and reduced cell-associated HIV-1 in a dose- and phospholipase D1-dependent manner. Genetic or pharmacological inhibition of autophagy ablated this effect. Thus, we can use TNP as therapeutic agents to neutralize cell-free HIV-1 and to target HIV-1 gp120-expressing cells to decrease the HIV-1 reservoir. IMPORTANCE HIV-1 is a major global health challenge. The development of an effective vaccine and/or a therapeutic cure is a top priority. The creation of vaccines that focus an antibody response toward a particular epitope of a protein has shown promise, but the genetic diversity of HIV-1 hinders this progress. Here we developed an approach using nanoengineered CD4+ T cell membrane-coated nanoparticles (TNP). Not only do TNP effectively neutralize all strains of HIV-1, but they also selectively bind to infected cells and decrease the release of HIV-1 particles through an autophagy-dependent mechanism with no drug-induced off-target or cytotoxic effects on bystander cells.
format	article
author	Gang Zhang Grant R. Campbell Qiangzhe Zhang Erin Maule Jonathan Hanna Weiwei Gao Liangfang Zhang Stephen A. Spector
author_facet	Gang Zhang Grant R. Campbell Qiangzhe Zhang Erin Maule Jonathan Hanna Weiwei Gao Liangfang Zhang Stephen A. Spector
author_sort	Gang Zhang
title	CD4<sup>+</sup> T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy
title_short	CD4<sup>+</sup> T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy
title_full	CD4<sup>+</sup> T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy
title_fullStr	CD4<sup>+</sup> T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy
title_full_unstemmed	CD4<sup>+</sup> T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy
title_sort	cd4<sup>+</sup> t cell-mimicking nanoparticles broadly neutralize hiv-1 and suppress viral replication through autophagy
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/bcd1ffecf9ad42c095dd956fce43381e
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CD4<sup>+</sup> T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy

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