Involvement of Src and Syk tyrosine kinases in HIV-1 transfer from dendritic cells to CD4+ T lymphocytes.
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.
Gilbert
Caroline
C
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, and Faculté de Médecine, Université Laval, 2705 Boulevard Laurier, Quebec, Canada.
Barat
Corinne
C
Cantin
Réjean
R
Tremblay
Michel J
MJ
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*; D009000:Monocytes / Q000276:immunology / Q000821:virology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000276:immunology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000276:immunology*; D034741:RNA, Small Interfering / Q000276:immunology / Q000494:pharmacology; D000072377:Syk Kinase
D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D011505:Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); C000606896:SYK protein, human; D000072377:Syk Kinase