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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-10-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00903-20 |
| _version_ | 1818434517901246464 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T16:38:15Z |
| format | Article |
| id | doaj.art-bcd1ffecf9ad42c095dd956fce43381e |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T16:38:15Z |
| publishDate | 2020-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-bcd1ffecf9ad42c095dd956fce43381e2022-12-21T22:54:24ZengAmerican Society for MicrobiologymBio2150-75112020-10-0111510.1128/mBio.00903-20CD4<sup>+</sup> T Cell-Mimicking Nanoparticles Broadly Neutralize HIV-1 and Suppress Viral Replication through AutophagyGang Zhang0Grant R. Campbell1Qiangzhe Zhang2Erin Maule3Jonathan Hanna4Weiwei Gao5Liangfang Zhang6Stephen A. Spector7Division of Infectious Diseases, Department of Pediatrics, University of California, San Diego, La Jolla, California, USADivision of Infectious Diseases, Department of Pediatrics, University of California, San Diego, La Jolla, California, USADepartment of Nanoengineering, University of California, San Diego, La Jolla, California, USADivision of Infectious Diseases, Department of Pediatrics, University of California, San Diego, La Jolla, California, USADivision of Infectious Diseases, Department of Pediatrics, University of California, San Diego, La Jolla, California, USADepartment of Nanoengineering, University of California, San Diego, La Jolla, California, USADepartment of Nanoengineering, University of California, San Diego, La Jolla, California, USADivision of Infectious Diseases, Department of Pediatrics, University of California, San Diego, La Jolla, California, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.00903-20HIVnanoparticleautophagyneutralizationCD4+ T cellmacrophage |
| spellingShingle | 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 mBio HIV nanoparticle autophagy neutralization CD4+ T cell macrophage |
| title | 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_short | 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 |
| topic | HIV nanoparticle autophagy neutralization CD4+ T cell macrophage |
| url | https://journals.asm.org/doi/10.1128/mBio.00903-20 |
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