Transmembrane Domain Membrane Proximal External Region but Not Surface Unit–Directed Broadly Neutralizing HIV-1 Antibodies Can Restrict Dendritic Cell–Mediated HIV-1 Trans-infection
| Autor: | Manish Sagar, Nora P. Ramirez, Suryaram Gummuluru, Behzad Etemad, Hisashi Akiyama, Ines Freitas |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
viruses Cell Lipopolysaccharide Receptors HIV Infections Biology HIV Antibodies HIV Envelope Protein gp120 Gp41 Virus Monocytes Cell membrane Major Articles and Brief Reports medicine Immunology and Allergy Humans Cells Cultured Cell-Free System virus diseases Antibodies Monoclonal Dendritic cell Dendritic Cells Virology Antibodies Neutralizing Coculture Techniques Transmembrane domain Infectious Diseases medicine.anatomical_structure Monoclonal biology.protein HIV-1 Antibody |
| Popis: | Background. Although broadly neutralizing antibodies (bNAbs) have been shown to block a diverse array of cell-free human immunodeficiency type 1 (HIV-1) infections, it remains unclear whether these antibodies exhibit similar potency against mature dendritic cell (mDC)–mediated HIV-1 trans-infection. Methods. Sensitivity to bNAbs targeting HIV-1 envelope surface unit gp120 (VRCO1, PG16, b12, and 2G12) and transmembrane domain gp41 (4E10 and 2F5) was examined for both cell-free and mDC-mediated infections of TZM-bl and CD4 1 T cells. Results. Compared with cell-free infection, mDC-mediated infection was significantly less susceptible to gp120-directed bNAbs for the majority of virus isolates. A b12 antigen-binding fragment blocked both cell-free and mDC-mediated infection with equal efficiency. In contrast, cell-free and mDC-associated viruses were equally sensitive to gp41-directed bNAbs. Anti-gp41 bNAbs bound to the surface of mDCs and localized at the mDC–T cell synaptic junctions in the absence of virus. Conclusions. Anti-gp41 bNAbs have the potential to inhibit mDC-mediated HIV-1 infection because they bind plasma membranes prior to the formation of an infectious synapse, positioning them to neutralize subsequent virus transfer. As opposed to gp120-directed antibodies, anti-gp41 bNAbs might prevent HIV-1 infection if transmission or spread at the initial site of invasion occurs from a DC-associated source. |
| Databáze: | OpenAIRE |
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