title: Bovine herpesvirus type 1 (BHV-1) UL49.5 luminal domain residues 30 to 32 are critical for MHC-I down-regulation in virus-infected cells.
abstract: Bovine herpesvirus type 1 (BHV-1) U(L)49.5 inhibits transporter associated with antigen processing (TAP) and down-regulates cell-surface expression of major histocompatibility complex (MHC) class I molecules to promote immune evasion. We have constructed a BHV-1 U(L)49.5 cytoplasmic tail (CT) null and several U(L)49.5 luminal domain mutants in the backbone of wild-type BHV-1 or BHV-1 U(L)49.5 CT- null viruses and determined their relative TAP mediated peptide transport inhibition and MHC-1 down-regulation properties compared with BHV-1 wt. Based on our results, the U(L)49.5 luminal domain residues 30-32 and U(L)49.5 CT residues, together, promote efficient TAP inhibition and MHC-I down-regulation functions. In vitro, BHV-1 U(L)49.5 Δ30-32 CT-null virus growth property was similar to that of BHV-1 wt and like the wt U(L)49.5, the mutant U(L)49.5 was incorporated in the virion envelope and it formed a complex with gM in the infected cells.
authors: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
authors: Huiyong
authors: H
authors: Wei
authors: Ying
authors: Y
authors: Wang
authors: Shafiqul I
authors: SI
authors: Chowdhury
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics; D007242:Herpesvirus 1, Bovine / Q000276:immunology / Q000472:pathogenicity*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics*; D057131:Immune Evasion; D007129:Immunoglobulin Gm Allotypes / Q000378:metabolism; D015678:Viral Structural Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D007129:Immunoglobulin Gm Allotypes; C073119:TAP1 protein, human; D015678:Viral Structural Proteins; C434023:tegument protein VP22, bovine herpesvirus 1