PMID- 26584215 OWN - NLM STAT- MEDLINE DCOM- 20160425 LR - 20151215 IS - 1096-0341 (Electronic) IS - 0042-6822 (Linking) VI - 487 DP - 2016 Jan TI - Hemopoietic cell kinase (Hck) and p21-activated kinase 2 (PAK2) are involved in the down-regulation of CD1a lipid antigen presentation by HIV-1 Nef in dendritic cells. PG - 285-95 LID - S0042-6822(15)00451-1 [pii] LID - 10.1016/j.virol.2015.10.023 [doi] AB - Dendritic cells (DCs) play a major role in in vivo pathogenesis of HIV-1 infection. Therefore, DCs may provide a promising strategy to control and eventually overcome the fatal infection. Especially, immature DCs express all CD1s, the non-MHC lipid antigen -presenting molecules, and HIV-1 Nef down-regulates CD1 expression besides MHC. Moreover, CD1d-restricted CD4(+) NKT cells are infected by HIV-1, reducing the number of these cells in HIV-1-infected individuals. To understand the exact role of DCs and CD1-mediated immune response during HIV-1 infection, Nef down-regulation of CD1a-restricted lipid/glycolipid Ag presentation in iDCs was analyzed. We demonstrated the involvement of the association of Nef with hemopoietic cell kinase (Hck) and p21-activated kinase 2 (PAK2), and that Hck, which is expressed strongly in iDCs, augmented this mutual interaction. Hck might be another therapeutic target to preserve the function of HIV-1 infected DCs, which are potential reservoirs of HIV-1 even after antiretroviral therapy. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Shinya, Eiji AU - Shinya E AD - Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo city, Tokyo 113-8602, Japan. FAU - Shimizu, Masumi AU - Shimizu M AD - Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo city, Tokyo 113-8602, Japan. FAU - Owaki, Atsuko AU - Owaki A AD - Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo city, Tokyo 113-8602, Japan. FAU - Paoletti, Samantha AU - Paoletti S AD - Experimental Immunology, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland. FAU - Mori, Lucia AU - Mori L AD - Experimental Immunology, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland. FAU - De Libero, Gennaro AU - De Libero G AD - Experimental Immunology, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland. FAU - Takahashi, Hidemi AU - Takahashi H AD - Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo city, Tokyo 113-8602, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151114 PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (Antigens, CD1) RN - 0 (CD1a antigen) RN - 0 (nef Gene Products, Human Immunodeficiency Virus) RN - 0 (nef protein, Human immunodeficiency virus 1) RN - EC 2.7.10.2 (HCK protein, human) RN - EC 2.7.10.2 (Proto-Oncogene Proteins c-hck) RN - EC 2.7.11.1 (PAK2 protein, human) RN - EC 2.7.11.1 (p21-Activated Kinases) SB - IM MH - Antigen Presentation/*immunology MH - Antigens, CD1/biosynthesis/*immunology MH - Cells, Cultured MH - Dendritic Cells/*immunology MH - Down-Regulation MH - HIV Infections/immunology/virology MH - HIV-1/immunology/pathogenicity MH - Humans MH - Proto-Oncogene Proteins c-hck/*metabolism MH - nef Gene Products, Human Immunodeficiency Virus/genetics/*immunology MH - p21-Activated Kinases/*metabolism OTO - NOTNLM OT - CD1a OT - Dendritic cells OT - HIV-1 Nef OT - Hemopoietic cell kinase OT - Lipid antigens OT - P-21 activated kinase 2 OT - Sulfatide EDAT- 2015/11/20 06:00 MHDA- 2016/04/26 06:00 CRDT- 2015/11/20 06:00 PHST- 2015/07/23 00:00 [received] PHST- 2015/10/21 00:00 [revised] PHST- 2015/10/24 00:00 [accepted] PHST- 2015/11/20 06:00 [entrez] PHST- 2015/11/20 06:00 [pubmed] PHST- 2016/04/26 06:00 [medline] AID - S0042-6822(15)00451-1 [pii] AID - 10.1016/j.virol.2015.10.023 [doi] PST - ppublish SO - Virology. 2016 Jan;487:285-95. doi: 10.1016/j.virol.2015.10.023. Epub 2015 Nov 14.