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Centre de Recherche en Infectiologie, Centre Hospitalier de l’Université Laval, and Faculté de Médecine, Université Laval, Quebec, Canada
Dendritic cells (DCs) are considered as key mediators of the early events in HIV-1 infection at mucosal sites. Although several aspects of the complex interactions between DCs and HIV-1 have been elucidated, there are still basic questions that remain to be answered about DCs/HIV-1 interplay. In this study, we examined the contribution of nonreceptor TKs in the known ability of DCs to efficiently transfer HIV-1 to CD4+ T cells in trans. Experiments performed with specific inhibitors of Src and Syk family members indicate that these tyrosine kinases (TKs) are participating to HIV-1 transfer from immature monocyte-derived DCs (IM-MDDCs) to autologous CD4+ T cells. Experiments with IM-MDDCs transfected with small interfering RNAs targeting Lyn and Syk confirmed the importance of these nonreceptor TKs in HIV-1 transmission. The Src- and Syk-mediated effect on virus transfer was linked with infection of IM-MDDCs in cis-as monitored by quantifying integrated viral DNA and de novo virus production. The process of HIV-1 transmission from IM-MDDCs to CD4+ T cells was unaffected following treatment with protein kinase C and protein kinase A inhibitors. These data suggest that Src and Syk TKs play a functional role in productive HIV-1 infection of IM-MDDCs. Additional work is needed to facilitate our comprehension of the various mechanisms underlying the exact contribution of Src and Syk TKs to this phenomenon.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was financially supported by operating grants to M.J.T. from the Canadian Foundation for AIDS Research (Grant 015 026) and Canadian Institutes of Health Research under the HIV/AIDS Research Program (Grant MOP-79542). C.G. is the recipient of a fellowship award from the Canadian Institutes of Health Research HIV/AIDS Research Program. J.M.T. holds the Tier 1 Canada Research Chair in Immuno-Retrovirology.
2 Address correspondence and reprint requests to Dr. Michel J. Tremblay, Laboratoire d’Immuno-Rétrovirologie Humaine, Centre de Recherche en Infectiologie, RC709, 2705 Boulevard Laurier, Quebec G1V 4G2, Canada. E-mail address: michel.j.tremblay{at}crchul.ulaval.ca
3 Abbreviations used in this paper: DC, dendritic cell; DC-SIGN, DC-specific ICAM3-grabbing nonintegrin; IM-MDDC, immature monocyte-derived DC; M-MDDC, mature monocyte-derived DC; MR, mannose receptor; PKA, protein kinase A; PKC, protein kinase C; siRNA, small interfering RNA; PP2, pyrazolopyrimidine.
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  A. A. Lambert, C. Gilbert, M. Richard, A. D. Beaulieu, and M. J. Tremblay The C-type lectin surface receptor DCIR acts as a new attachment factor for HIV-1 in dendritic cells and contributes to trans- and cis-infection pathways Blood, August 15, 2008; 112(4): 1299 - 1307. [Abstract] [Full Text] [PDF]
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