An endocytic YXXΦ (YRRF) cargo sorting motif in the cytoplasmic tail of murine cytomegalovirus AP2 ‘adapter adapter-protein m04/gp34 antagonizes virus evasion of natural killer cells

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• 作者：Annette Fink ; Franziska Blaum ; Marina Babic Cac…
• 关键词：Adapter protein (AP2) ; Cargo sorting ; Clathrin ; mediated endocytosis ; Endocytosis motif ; Immune evasion ; Tyrosine ; based motif YXXΦ
• 刊名：Medical Microbiology and Immunology
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：204
• 期：3
• 页码：383-394
• 全文大小：1,684 KB
• 参考文献：1.Reddehase MJ (2002) Antigens and immunoevasins: opponents in cytomegalovirus immune surveillance. Nat Rev Immunol 2:831-44View Article PubMed
  2.Doom C, Hill AB (2008) MHC class I immune evasion in MCMV infection. Med Microbiol Immunol 197:191-04View Article PubMed
  3.Lemmermann NA, B?hm V, Holtappels R, Reddehase MJ (2011) In vivo impact of cytomegalovirus evasion of CD8 T-cell immunity: facts and thoughts based on murine models. Virus Res 157:161-74View Article PubMed
  4.Lemmermann NA, Fink A, Podlech J, Ebert S, Wilhelmi V, B?hm V, Holtappels R, Reddehase MJ (2012) Murine cytomegalovirus immune evasion proteins operative in the MHC class I pathway of antigen processing and presentation: state of knowledge, revisions, and questions. Med Microbiol Immunol 201:497-12View Article PubMed
  5.Hansen TH, Bouvier M (2009) MHC class I antigen presentation: learning from viral evasion strategies. Nat Rev Immunol 9:503-13View Article PubMed
  6.Del Val M, Hengel H, Hacker H, Hartlaub U, Ruppert T, Lucin P, Koszinowski UH (1992) Cytomegalovirus prevents antigen presentation blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment. J Exp Med 172:729-38View Article
  7.Ziegler H, Thale R, Lucin P, Muranyi W, Flohr T, Hengel H, Farrell H, Rawlinson W, Koszinowski UH (1997) A mouse cytomegalovirus glycoprotein retains MHC class I complexes in the ERGIC/cis-Golgi compartments. Immunity 6:57-6View Article PubMed
  8.Ziegler H, Muranyi W, Burgert HG, Kremmer E, Koszinowski UH (2000) The luminal part of the murine cytomegalovirus glycoprotein gp40 catalyzes the retention of MHC class I molecules. EMBO J 19:870-81View Article PubMed Central PubMed
  9.Krmpotic A, Messerle M, Crnkovic-Mertens I, Polic B, Jonjic S, Koszinowski UH (1999) The immunoevasive function encoded by the mouse cytomegalovirus gene m152 protects the virus against T cell control in vivo. J Exp Med 190:1285-296View Article PubMed Central PubMed
  10.Holtappels R, Podlech J, Pahl-Seibert M-F, Jülch M, Thomas D, Simon CO, Wagner M, Reddehase MJ (2004) Cytomegalovirus misleads its host by priming of CD8 T cells specific for an epitope not presented in infected tissues. J Exp Med 199:131-36View Article PubMed Central PubMed
  11.Lemmermann NA, Gergely K, B?hm V, Deegen P, D?ubner T, Reddehase MJ (2010) Immune evasion proteins of murine cytomegalovirus preferentially affect cell surface display of recently generated peptide presentation complexes. J Virol 84:1221-236View Article PubMed Central PubMed
  12.Lodoen M, Ogasawara K, Hamerman J, Arase H, Houchins J, Mocarski E, Lanier L (2003) NKG2D-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules. J Exp Med 197:1245-253View Article PubMed Central PubMed
  13.Zhi L, Mans J, Paskow MJ, Brown PH, Schuck P, Jonjic S, Natarajan K, Margulies DH (2010) Direct interaction of the mouse cytomegalovirus m152/gp40 immunoevasin with RAE-1 isoforms. Biochemistry 49:2443-453View Article PubMed Central PubMed
  14.Krmpotic A, Busch DH, Bubic I, Gebhardt F, Hengel H, Hasan M, Scalzo AA, Koszinowski UH, Jonjic S (2002) MCMV glycoprotein gp40 confers virus resistance to CD8+ T cells and NK cells in vivo. Nat Immunol 3:529-35View Article PubMed
  15.Wang R, Natarajan K, Revilleza M, Boyd L, Zhi L, Zhao H, Robinson H, Margulies D (2012) Structural basis of mouse cytomegalovirus m152/gp40 interaction with RAE1γ reveals a paradigm for MHC/MHC interaction in immune evasion. Proc Natl Acad Sci USA 109:E3578–E3587View Article PubMed Central PubMed
  16.Fink A, Renzaho A, Reddehase M, Lemmermann NAW (2013) The p36 isoform of murine cytomegalovirus m152 protein suffices for mediating innate and adaptive immune evasion. Viruses 5:3171-191View Article PubMed Central PubMed
  17.Lenac T, Arapovic J, Traven L, Krmpotic A, Jonjic S (2008) Murine cytomegalovirus regulation of NKG2D ligands. Med Microbiol Immunol 197:159-66View Article PubMed
  18.Rawlinson W, Farrell H, Barrell B (1996) Analysis of the complete DNA sequence of murine cytomegalovirus. J Virol 70:8833-849PubMed Central PubMed
  19.Kleijnen MF, Huppa JB, Lucin P, Mukherjee S, Farrell H, Campbell AE, Koszinowski UH, Hill AB, Ploegh HL (1997) A mouse cytomegalovirus glycoprotein, gp34, forms a complex with folded class I MHC molecules in the ER which is not retained but is transported to the cell surface. EMBO J 16:685-94View Article PubMed Central PubMed
  20.Reusch U, Muranyi W, Lucin P, Burgert HG, Hengel H, Koszinowski UH (1999) A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation. EMBO J 18:1081-091View Article PubMed Central PubMed
  21.Reusch U, Bernhard O, Koszinowski UH, Schu P (2002) AP-1A and AP-3A lysosomal sorting functions. Traffic 3:752-61View Article PubMed
  22.Oldridge J, Marsh M (1998) Nef-an adap
• 作者单位：Annette Fink (1)
  Franziska Blaum (1)
  Marina Babic Cac (2) (3)
  Stefan Ebert (1) (4)
  Niels A. W. Lemmermann (1)
  Matthias J. Reddehase (1)
  
  1. Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz and Research Center for Immunotherapy (FZI), Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131, Mainz, Germany
  2. Department of Histology and Embryology, School of Medicine, University of Rijeka, Rijeka, Croatia
  3. German Rheumatism Research Centre, Innate Immunity Group, Berlin, Germany
  4. Section for Experimental Tumor Immunology, Department for Obstetrics and Gynaecology, University of Wuerzburg Medical School, Würzburg, Germany
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Medical Microbiology
  Immunology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1831

文摘

Viruses have evolved proteins that bind immunologically relevant cargo molecules at the cell surface for their downmodulation by internalization. Via a tyrosine-based sorting motif YXXΦ in their cytoplasmic tails, they link the bound cargo to the cellular adapter protein-2 (AP2), thereby sorting it into clathrin-triskelion-coated pits for accelerated endocytosis. Downmodulation of CD4 molecules by lentiviral protein NEF represents the most prominent example. Based on connecting cargo to cellular adapter molecules, such specialized viral proteins have been referred to as ‘connectors-or ‘adapter adapters.-Murine cytomegalovirus glycoprotein m04/gp34 binds stably to MHC class-I (MHC-I) molecules and suspiciously carries a canonical YXXΦ endocytosis motif YRRF in its cytoplasmic tail. Disconnection from AP2 by motif mutation ARRF should retain m04-MHC-I complexes at the cell surface and result in an enhanced silencing of natural killer (NK) cells, which recognize them via inhibitory receptors. We have tested this prediction with a recombinant virus in which the AP2 motif is selectively destroyed by point mutation Y248A, and compared this with the deletion of the complete protein in a Δm04 mutant. Phenotypes were antithetical in that loss of AP2-binding?enhanced NK cell silencing, whereas absence of m04-MHC-I released them from silencing. We thus conclude that AP2-binding antagonizes NK cell silencing by enhancing endocytosis of the inhibitory ligand m04-MHC-I. Based on a screen for tyrosine-based endocytic motifs in cytoplasmic tail sequences, we propose here the new hypothesis that most proteins of the m02-em class="EmphasisTypeItalic">m16 gene family serve as ‘adapter adapters,-each selecting its specific cell surface cargo for clathrin-assisted internalization.