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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
- Publication Year :
- 2012
- Publisher :
- Oxford University Press, 2012.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....e86793c1b8e5938a60403d689b2c8c20