%0 Journal Article
%T Extracellular ATP reduces HIV-1 transfer from immature dendritic cells to CD4+ T lymphocytes
%A Corinne Barat
%A Caroline Gilbert
%A Michael Imbeault
%A Michel J Tremblay
%J Retrovirology
%D 2008
%I BioMed Central
%R 10.1186/1742-4690-5-30
%X In this study, we show that extracellular ATP reduces HIV-1 transfer from immature monocyte-derived DCs (iDCs) to autologous CD4+ T cells. This observed decrease in viral replication was related to a lower proportion of infected CD4+ T cells following transfer, and was seen with both X4- and R5-tropic isolates of HIV-1. Extracellular ATP had no effect on direct CD4+ T cell infection as well as on productive HIV-1 infection of iDCs. These observations indicate that extracellular ATP affects HIV-1 infection of CD4+ T cells in trans with no effect on de novo virus production by iDCs. Additional experiments suggest that extracellular ATP might modulate the trafficking pathway of internalized virions within iDCs leading to an increased lysosomal degradation, which could be partly responsible for the decreased HIV-1 transmission.These results suggest that extracellular ATP can act as a factor controlling HIV-1 propagation.Dendritic cells (DCs) are crucial in generating a virus-specific immune response since they are recognized as the most potent antigen-presenting cells of the immune system, yet they also play a pivotal role in establishment and dissemination of HIV-1 infection. Indeed, HIV-1 exploits the migratory ability of DCs to gain access to CD4+ T lymphocytes in lymphoid tissues. DCs, particularly immature DCs (iDCs) that reside in peripheral mucosal tissues, are among the first target cells for the virus. The reported low levels of CD4 and chemokine co-receptors CXCR4 and CCR5 on DCs are probably responsible for their weaker susceptibility to productive HIV-1 infection in vitro as compared to CD4+ T cells [1,2]. It has been demonstrated that interactions between the external HIV-1 envelope and C-type lectin receptors such as DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) [3,4], mannose receptor (MR) (CD206) and galactosyl ceramide [5] result in an efficient capture of viral particles. Following interactions with the viral entity, DCs
%U http://www.retrovirology.com/content/5/1/30