PMID- 17312130 OWN - NLM STAT- MEDLINE DCOM- 20070424 LR - 20190516 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 178 IP - 5 DP - 2007 Mar 1 TI - Involvement of Src and Syk tyrosine kinases in HIV-1 transfer from dendritic cells to CD4+ T lymphocytes. PG - 2862-71 AB - 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. FAU - Gilbert, Caroline AU - Gilbert C AD - Centre de Recherche en Infectiologie, Centre Hospitalier de l'Universite Laval, and Faculte de Medecine, Universite Laval, 2705 Boulevard Laurier, Quebec, Canada. FAU - Barat, Corinne AU - Barat C FAU - Cantin, Rejean AU - Cantin R FAU - Tremblay, Michel J AU - Tremblay MJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Protein Kinase Inhibitors) RN - 0 (RNA, Small Interfering) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src)) RN - EC 2.7.10.2 (SYK protein, human) RN - EC 2.7.10.2 (Syk Kinase) SB - IM MH - CD4-Positive T-Lymphocytes/*immunology/virology MH - Cells, Cultured MH - Dendritic Cells/*immunology/virology MH - HIV Infections/immunology/*transmission MH - HIV-1/*immunology MH - Humans MH - Intracellular Signaling Peptides and Proteins/antagonists & inhibitors/*immunology MH - Monocytes/immunology/virology MH - Protein Kinase Inhibitors/pharmacology MH - Protein-Tyrosine Kinases/antagonists & inhibitors/*immunology MH - Proto-Oncogene Proteins pp60(c-src)/*immunology MH - RNA, Small Interfering/immunology/pharmacology MH - Syk Kinase EDAT- 2007/02/22 09:00 MHDA- 2007/04/25 09:00 CRDT- 2007/02/22 09:00 PHST- 2007/02/22 09:00 [pubmed] PHST- 2007/04/25 09:00 [medline] PHST- 2007/02/22 09:00 [entrez] AID - 178/5/2862 [pii] AID - 10.4049/jimmunol.178.5.2862 [doi] PST - ppublish SO - J Immunol. 2007 Mar 1;178(5):2862-71. doi: 10.4049/jimmunol.178.5.2862.