Neutralizing antibodies inhibit HIV-1 transfer from primary dendritic cells to autologous CD4 T lymphocytes

Neutralizing IgG at the Portal of Infection Mediates Protection against Vaginal Simian/Human Immunodeficiency Virus Challenge

“…Blocking experiments confirmed the importance of Fc␥-R engagement by 2F5 in inhibiting HIV replication in MDDC-T cell cocultures. These data are in agreement with previous studies showing 2F5 IgG as highly active in preventing HIV-1 infection of immature MDM and MDDCs relative to 2F5 Fab (25)(26)(27)57) and the importance of Fc␥-R engagement in reducing DC-mediated trans-infection of CD4 T cells (58). Interestingly, the inhibitory activities (IC 50 ) of 2F5 IgG and Fab were similar in cervical explant cultures despite such tissue containing a high density of macrophages and dendritic cells.…”

“…However, the Fc portion of 2F5 IgG did affect dissemination of virus by migratory cells emigrating from tissue explants. This reflects earlier observations that binding of neutralizing antibodies to Fc␥-Rs on DC significantly augments the inhibition of HIV replication in DC-CD4 T cell clusters (58). This mechanism might affect viral dissemination in vivo and have an influence on peak viral load or subsequent viral set point.…”

Broadly Neutralizing Antibody VRC01 Prevents HIV-1 Transmission from Plasmacytoid Dendritic Cells to CD4 T Lymphocytes

“…These results indicate that HIV-1 transfer from pDC to CD4 T cells is inhibited to a similar extent as cell-free virus particles in these culture conditions. A similar inhibition was previously observed between cellfree and HIV-1 transfer from MoDC to CD4 T cells (31) and confirmed in this study. Interestingly, a similar inhibitory activity of VRC01 was recently reported for the HIV-1 transmission from macrophages to T cells (43).…”

“…Despite low HIV-1 replication in pDC, these cells efficiently transfer HIV-1 to adjacent CD4 T lymphocytes (27)(28)(29). HIV-1 transfer has been well described in immature monocyte-derived dendritic cells (MoDC) as a two-phase transfer with first a direct cell-to-cell passage of virus in trans followed by cis-infection with newly produced viruses (30,31; reviewed in references [32][33][34]. Here, we aim to analyze early phases of HIV-1 transfer from primary pDC to CD4 T lymphocytes and the effect of bNAb VRC01 on this transfer.…”

Les anticorps anti-VIH

“…Le mécanisme d'inhibition n'a pas encore été clairement identifié même s'il a été proposé que les complexes immuns, fixés aux cellules effectrices par l'intermédiaire des RFcγ, seraient phagocytés puis dégradés dans des lysosomes spécifiques. La fixation des anticorps sur les RFc de cellules effectrices peut aussi déclencher l'activation d'autres mécanismes fonctionnels qui pourraient conduire à une diminution de la réplication virale, comme : -l'induction de cytokines et/ou de chimiokines antivirales [15] ; -la maturation des cellules présentatrices d'antigènes qui favoriserait la restriction virale par des mécanismes postfusion [16]. …”