Journal
BLOOD
Volume 120, Issue 18, Pages 3708-3717Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2012-03-418913
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Funding
- EuroNeut41 [FP7-HELTH-2007-A-201038]
- EuroPrise [LSHP-CT-2006-037611]
- Sidaction
- Dormeur Investment Service Ltd
- Agence Nationale de Recherche sur le Sida
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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 Fc gamma Rs 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. (Blood. 2012;120(18):3708-3717)
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