ArticleCellular & molecular immunology2021
Generation of HIV-resistant cells with a single-domain antibody: implications for HIV-1 gene therapy.
Article in Cellular & molecular immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Protein Engineering and Drug Discovery: Importance, Methodologies, Challenges, and Prospects.Biomolecules · 2025Review
- Addition of a short HIV-1 fusion-inhibitory peptide to PRO 140 antibody dramatically increases its antiviral breadth and potency.Journal of virology · 2025Article
- Nanobodies in the fight against infectious diseases: repurposing nature's tiny weapons.World journal of microbiology & biotechnology · 2024Review
- Cell membrane anchoring strategies for HIV gene therapy.Cellular & molecular immunology · 2023Article
- Therapeutic applications of nanobodies against SARS-CoV-2 and other viral infections: Current update.International journal of biological macromolecules · 2023Review
- Cell membrane-anchored anti-HIV single-chain antibodies and bifunctional inhibitors targeting the gp41 fusion protein: new strategies for HIV gene therapy.Emerging microbes & infections · 2022Article
- Single-Chain Variable Fragments of Broadly Neutralizing Antibodies Prevent HIV Cell-Cell Transmission.Journal of virology · 2022Article
- Article
- The TZM-bl Reporter Cell Line Expresses Kynureninase That Can Neutralize 2F5-like Antibodies in the HIV-1 Neutralization Assay.International journal of molecular sciences · 2022Article
- Design of a Bispecific HIV Entry Inhibitor Targeting the Cell Receptor CD4 and Viral Fusion Protein Gp41.Frontiers in cellular and infection microbiology · 2022Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cure or functional cure of the "Berlin patient" and "London patient" indicates that infusion of HIV-resistant cells could be a viable treatment strategy. Very recently, we genetically linked a short-peptide fusion inhibitor with a glycosylphosphatidylinositol (GPI) attachment signal, rendering modified cells fully resistant to HIV infection. In this study, GPI-anchored m36.4, a single-domain antibody (nanobody) targeting the coreceptor-binding site of gp120, was constructed with a lentiviral vector. We verified that m36.4 was efficiently expressed on the plasma membrane of transduced TZM-bl cells and targeted lipid raft sites without affecting the expression of HIV receptors (CD4, CCR5, and CXCR4). Significantly, TZM-bl cells expressing GPI-m36.4 were highly resistant to infection with divergent HIV-1 subtypes and potently blocked HIV-1 envelope-mediated cell-cell fusion and cell-cell viral transmission. Furthermore, we showed that GPI-m36.4-modified human CEMss-CCR5 cells were nonpermissive to both CCR5- and CXCR4-tropic HIV-1 isolates and displayed a strong survival advantage over unmodified cells. It was found that GPI-m36.4 could also impair HIV-1 Env processing and viral infectivity in transduced cells, underlying a multifaceted mechanism of antiviral action. In conclusion, our studies characterize m36.4 as a powerful nanobody that can generate HIV-resistant cells, offering a novel gene therapy approach that can be used alone or in combination.
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Registered trials
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