Virology. 2016 Jan;487:285-95.

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.

 

Shinya E1, Shimizu M1, Owaki A1, Paoletti S2, Mori L2, De Libero G2, Takahashi H1.
  • 1Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo city, Tokyo 113-8602, Japan.
  • 2Experimental Immunology, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel,¬†Switzerland.

 

Abstract

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.

KEYWORDS: CD1a; Dendritic cells; HIV-1 Nef; Hemopoietic cell kinase; Lipid antigens; P-21 activated kinase 2; Sulfatide

PMID: 26584215

 

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