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CD4(+) T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy
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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492730/ https://www.ncbi.nlm.nih.gov/pubmed/32934078 http://dx.doi.org/10.1128/mBio.00903-20 |
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author | Zhang, Gang Campbell, Grant R. Zhang, Qiangzhe Maule, Erin Hanna, Jonathan Gao, Weiwei Zhang, Liangfang Spector, Stephen A. |
author_facet | Zhang, Gang Campbell, Grant R. Zhang, Qiangzhe Maule, Erin Hanna, Jonathan Gao, Weiwei Zhang, Liangfang Spector, Stephen A. |
author_sort | Zhang, Gang |
collection | PubMed |
description | 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 (IC(80)) 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. |
format | Online Article Text |
id | pubmed-7492730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-74927302020-09-25 CD4(+) T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy Zhang, Gang Campbell, Grant R. Zhang, Qiangzhe Maule, Erin Hanna, Jonathan Gao, Weiwei Zhang, Liangfang Spector, Stephen A. mBio Research Article 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 (IC(80)) 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. American Society for Microbiology 2020-09-15 /pmc/articles/PMC7492730/ /pubmed/32934078 http://dx.doi.org/10.1128/mBio.00903-20 Text en Copyright © 2020 Zhang et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Zhang, Gang Campbell, Grant R. Zhang, Qiangzhe Maule, Erin Hanna, Jonathan Gao, Weiwei Zhang, Liangfang Spector, Stephen A. CD4(+) T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy |
title | CD4(+) T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy |
title_full | CD4(+) T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy |
title_fullStr | CD4(+) T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy |
title_full_unstemmed | CD4(+) T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy |
title_short | CD4(+) T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through Autophagy |
title_sort | cd4(+) t cell-mimicking nanoparticles broadly neutralize hiv-1 and suppress viral replication through autophagy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492730/ https://www.ncbi.nlm.nih.gov/pubmed/32934078 http://dx.doi.org/10.1128/mBio.00903-20 |
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