Dendritic Cell-Lymphocyte Crosstalk Downregulates Host Restriction Factor SAMHD1 and Stimulates HIV-1 Replication in Dendritic Cells

SU, B; BIEDMA, M.E.; LEDERLE, A; PERESSIN, M; LAMBOTIN, M; PROUST, A; DECOVILLE, T; SCHMIDT, S; LAUMOND, G; MOOG, C

JOURNAL OF VIROLOGY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2014

0022-538X

HIV-1 replication in dendritic cells (DCs) is restricted by SAMHD1. This factor is counteracted by the viral protein Vpx; Vpx is found in HIV-2 and SIVsm/SIVmac, but is absent from HIV-1. We previously observed that HIV-1 replication in immature DCs is stimulated by cocultivation with primary T/B lymphocytes, suggesting that HIV-1 restriction in DCs may be overcome in coculture conditions. Here, we aimed to decipher the mechanism of SAMHD1-mediated restriction in DC/lymphocyte coculture. We found that coculture with lymphocytes downregulated SAMHD1 expression and was associated with an increased HIV-1 replication in DCs. Moreover, in infected DC/T lymphocyte cocultures, DCs acquired maturation status and secreted IFN-α. The blockade of DC/lymphocyte crosstalk by anti-ICAM-1 antibody markedly inhibited the stimulation of HIV-1 replication and prevented the downregulation of SAMHD1 expression in cocultured DCs. These results demonstrate that, in contrast to purified DCs, crosstalk with lymphocytes downregulates SAMHD1 expression in DCs, triggering HIV-1 replication and an antiviral immune response. Therefore, HIV-1 replication and immune sensing by DCs should be investigated in more physiologically relevant models of DC/lymphocyte coculture.