PMID- 20530791 OWN - NLM STAT- MEDLINE DCOM- 20101029 LR - 20211020 IS - 1528-0020 (Electronic) IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 116 IP - 11 DP - 2010 Sep 16 TI - Inhibition of lipid antigen presentation in dendritic cells by HIV-1 Vpu interference with CD1d recycling from endosomal compartments. PG - 1876-84 LID - 10.1182/blood-2009-09-243667 [doi] AB - Dendritic cells (DCs) play an important role in viral infections both as initiators of immunity and as viral targets. Interaction between DCs and the innate-like CD1d-restricted natural killer T (NKT) cells results in the mutual activation of both cells and the subsequent initiation of cellular immune responses. Here, we show that HIV-1 inhibits the surface expression of CD1d in productively infected DCs and identify this as a novel activity of the HIV-1 vpu gene product. Interestingly, the viral protein U (Vpu) does not enhance constitutive CD1d endocytosis or induce rapid CD1d degradation. Instead, the Vpu protein interacts with CD1d and suppresses its recycling from endosomal compartments to the cell surface by retaining CD1d in early endosomes. This interference with the CD1d antigen presentation pathway strongly inhibits the ability of infected DCs to activate CD1d-restricted NKT cells. Given that the interaction with CD1d-expressing DCs is central to the ability of NKT cells to regulate immunity, these data suggest that interference with the CD1d antigen presentation pathway represents an HIV-1 strategy to evade innate cellular immune responses and imply a role for the innate-like CD1d-restricted NKT cells in the host defense against HIV-1. FAU - Moll, Markus AU - Moll M AD - Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. markus.moll@ki.se FAU - Andersson, Sofia K AU - Andersson SK FAU - Smed-Sorensen, Anna AU - Smed-Sorensen A FAU - Sandberg, Johan K AU - Sandberg JK LA - eng GR - R01 AI052731/AI/NIAID NIH HHS/United States GR - R37 AI052731/AI/NIAID NIH HHS/United States GR - AI52731/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20100608 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antigens, CD1) RN - 0 (Antigens, CD1d) RN - 0 (Human Immunodeficiency Virus Proteins) RN - 0 (Lipids) RN - 0 (Viral Regulatory and Accessory Proteins) RN - 0 (vpu protein, Human immunodeficiency virus 1) RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Antigen Presentation/*immunology MH - Antigens, CD1/metabolism MH - Antigens, CD1d/genetics/*immunology/metabolism MH - Blotting, Western MH - Cell Line MH - Cell Membrane/immunology/metabolism MH - Cells, Cultured MH - Dendritic Cells/*immunology/metabolism/virology MH - Endocytosis/immunology MH - Endosomes/*immunology/metabolism MH - Green Fluorescent Proteins/genetics/metabolism MH - HIV-1/genetics/immunology/metabolism MH - Human Immunodeficiency Virus Proteins/genetics/*immunology/metabolism MH - Humans MH - Lipids/immunology MH - Lymphocyte Activation/immunology MH - Microscopy, Fluorescence MH - Natural Killer T-Cells/immunology/metabolism MH - Protein Binding MH - Viral Regulatory and Accessory Proteins/genetics/*immunology/metabolism PMC - PMC3173986 EDAT- 2010/06/10 06:00 MHDA- 2010/10/30 06:00 PMCR- 2011/09/16 CRDT- 2010/06/10 06:00 PHST- 2010/06/10 06:00 [entrez] PHST- 2010/06/10 06:00 [pubmed] PHST- 2010/10/30 06:00 [medline] PHST- 2011/09/16 00:00 [pmc-release] AID - S0006-4971(20)32990-6 [pii] AID - 2009/243667 [pii] AID - 10.1182/blood-2009-09-243667 [doi] PST - ppublish SO - Blood. 2010 Sep 16;116(11):1876-84. doi: 10.1182/blood-2009-09-243667. Epub 2010 Jun 8.