title: Neutralizing antibodies inhibit HIV-1 transfer from primary dendritic cells to autologous CD4 T lymphocytes.
abstract: Dendritic cells (DCs) support only low levels of HIV-1 replication, but have been shown to transfer infectious viral particles highly efficiently to neighboring permissive CD4 T lymphocytes. This mode of cell-to-cell HIV-1 spread may be a predominant mode of infection and dissemination. In the present study, we analyzed the kinetics of fusion, replication, and the ability of HIV-1-specific Abs to inhibit HIV-1 transfer from immature DCs to autologous CD4 T lymphocytes. We found that neutralizing mAbs prevented HIV-1 transfer to CD4 T lymphocytes in trans and in cis, whereas nonneutralizing Abs did not. Neutralizing Abs also significantly decreased HIV-1 replication in DCs, even when added 2 hours after HIV-1 infection. Interestingly, a similar inhibition of HIV-1 replication in DCs was detected with some nonneutralizing Abs and was correlated with DC maturation. We suggest that the binding of HIV-1-specific Abs to FcγRs leads to HIV-1 inhibition in DCs by triggering DC maturation. This efficient inhibition of HIV-1 transfer by Abs highlights the importance of inducing HIV-specific Abs by vaccination directly at the mucosal portal of HIV-1 entry to prevent early dissemination after sexual transmission.
authors.affiliation: Inserm U748, Université de Strasbourg, Strasbourg, France.
authors.forename: Bin
authors.initials: B
authors.lastname: Su
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lederle
authors.forename: Maryse
authors.initials: M
authors.lastname: Peressin
authors.forename: Marina Elizabeth
authors.initials: ME
authors.lastname: Biedma
authors.forename: Géraldine
authors.initials: G
authors.lastname: Laumond
authors.forename: Sylvie
authors.initials: S
authors.lastname: Schmidt
authors.forename: Thomas
authors.initials: T
authors.lastname: Decoville
authors.forename: Alizé
authors.initials: A
authors.lastname: Proust
authors.forename: Mélanie
authors.initials: M
authors.lastname: Lambotin
authors.forename: Vincent
authors.initials: V
authors.lastname: Holl
authors.forename: Christiane
authors.initials: C
authors.lastname: Moog
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000635:transmission* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans
chemical_list: D057134:Antibodies, Neutralizing