title: The p36 isoform of murine cytomegalovirus m152 protein suffices for mediating innate and adaptive immune evasion.
abstract: The MHC-class I (MHC-I)-like viral (MHC-Iv) m152 gene product of murine cytomegalovirus (mCMV) was the first immune evasion molecule described for a member of the β-subfamily of herpesviruses as a paradigm for analogous functions of human cytomegalovirus proteins. Notably, by interacting with classical MHC-I molecules and with MHC-I-like RAE1 family ligands of the activatory natural killer (NK) cell receptor NKG2D, it inhibits presentation of antigenic peptides to CD8 T cells and the NKG2D-dependent activation of NK cells, respectively, thus simultaneously interfering with adaptive and innate immune recognition of infected cells. Although the m152 gene product exists in differentially glycosylated isoforms whose individual contributions to immune evasion are unknown, it has entered the scientific literature as m152/gp40, based on the quantitatively most prominent isoform but with no functional justification. By construction of a recombinant mCMV in which all three N-glycosylation sites are mutated (N61Q, N208Q, and N241Q), we show here that N-linked glycosylation is not essential for functional interaction of the m152 immune evasion protein with either MHC-I or RAE1. These data add an important functional detail to recent structural analysis of the m152/RAE1g complex that has revealed N-glycosylations at positions Asn61 and Asn208 of m152 distant from the m152/RAE1g interface.
authors.forename: Annette
authors.initials: A
authors.lastname: Fink
authors.forename: Angeliqué
authors.initials: A
authors.lastname: Renzaho
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, Mainz D-55131, Germany. matthias.reddehase@uni-mainz.de.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Reddehase
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University Mainz, Obere Zahlbacher Str. 67, Mainz D-55131, Germany. lemmermann@uni-mainz.de.
authors.forename: Niels A W
authors.initials: NA
authors.lastname: Lemmermann
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006031:Glycosylation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D057131:Immune Evasion; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018146:Muromegalovirus / Q000276:immunology* / Q000502:physiology*; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000276:immunology*; D011499:Protein Processing, Post-Translational; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D034521:Nuclear Matrix-Associated Proteins; D029543:Nucleocytoplasmic Transport Proteins; D020033:Protein Isoforms; C490521:Rae1 protein, mouse; D014764:Viral Proteins; C104783:m152 protein, cytomegalovirus