110 MOLECULAR MECHANISMS REGULATING DCs-MEDIATED HIV-1 TRANSMISSION C Gilbert, C Barat, R Cantin, MJ Tremblay Dendritic cells (DCs) are considered as key mediators of the early events in human immunodeficiency virus type 1 (HIV-1) infection at mucosal sites. Although several aspects of the complex interactions between DCs and HIV-1 have been elucidated, there are still questions that remain answered about DC/HIV-1 interplay.
Centre de Recherche en Infectiologie, Montréal, Québec
Objectives: Here, we have investigated whether virion-incorporated host cell membrane proteins and signaling molecules can modulate the mechanism of HIV-1 transmission from DCs to autologous CD4+ T lymphocytes.
Methods: Using isogenic viruses either devoid or bearing host-derived adhesion molecules such as ICAM-1 and LFA-1 and/or pharmacological inhibitors.
Results: We show that HIV-1 transfer is increased; in manner depend on PKA and PKC for LFA-1-bearing virions as compared to virions lacking this adhesion molecule. Moreover, we showed that treatment with Srcs and Syk tyrosine kinase inhibitors enhance HIV-1 transfer. In both cases this increase is linked to a more important productive infection of IM-MDDCs. On the other hand DC treatment with ATP treatment decreases the amount of transferred virions without affecting infection of DCs. Finally HIV-1 transfer is affected by several compounds involved in virus uptake such as statin, macropinocytosis inhibitors and also by CCR5 antagonists.
Conclusions: Therefore, interactions between virus-bound host cell membrane protein with their ligands on the surface of DCs as well as various signaling and internalization pathways can influence the extent of HIV-1 transfer to CD4+ T lymphocytes. Altogether this study contributes to our comprehension of the various mechanisms underlying the complex interactions occurring between DCs and HIV-1.