title: Herpes simplex virus type 1 targets the MHC class II processing pathway for immune evasion.
abstract: HSV type 1 (HSV-1) has evolved numerous strategies for modifying immune responses that protect against infection. Important targets of HSV-1 infection are the MHC-encoded peptide receptors. Previous studies have shown that a helper T cell response and Ab production play important roles in controlling HSV-1 infection. The reduced capacity of infected B cells to stimulate CD4(+) T cells is beneficial for HSV-1 to evade immune defenses. We investigated the impact of HSV-1 infection on the MHCII processing pathway, which is critical to generate CD4(+) T cell help. HSV-1 infection targets the molecular coplayers of MHC class II processing, HLA-DR (DR), HLA-DM (DM), and invariant chain (Ii). HSV-1 infection strongly reduces expression of Ii, which impairs formation of SDS-resistant DR-peptide complexes. Residual activity of the MHC class II processing pathway is diminished by viral envelope glycoprotein B (gB). Binding of gB to DR competes with binding to Ii. In addition, we found gB associated with DM molecules. Both, gB-associated DR and DM heterodimers are exported from the endoplasmic reticulum, as indicated by carbohydrate maturation. Evaluation of DR, DM, and gB subcellular localization revealed abundant changes in intracellular distribution. DR-gB complexes are localized in subcellular vesicles and restrained from cell surface expression.
authors.affiliation: Section of Immunobiology, Institute for Molecular Physiology, University of Bonn, Bonn, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Neumann
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Eis-Hübinger
authors.forename: Norbert
authors.initials: N
authors.lastname: Koch
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D001667:Binding, Competitive / Q000276:immunology; D019556:COS Cells; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006056:Golgi Apparatus / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006681:HLA-D Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D021381:Protein Transport / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000378:metabolism; D014774:Virulence / Q000276:immunology
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C045084:invariant chain