Peptide transport activity of the transporter associated with antigen processing (TAP) is inhibited by an early protein of equine herpesvirus-1.
Equine herpesvirus-1 (EHV-1) downregulates surface expression of major histocompatibility complex (MHC) class I molecules on infected cells. The objective of this study was to investigate whether EHV-1 interferes with peptide translocation by the transporter associated with antigen processing (TAP) and to identify the proteins responsible. Using an in vitro transport assay, we showed that EHV-1 inhibited transport of peptides by TAP as early as 2 h post-infection (p.i). Complete shutdown of peptide transport was observed by 8 h p.i. Furthermore, pulse-chase experiments revealed that maturation of class I molecules in the endoplasmic reticulum (ER) was delayed in EHV-1-infected cells, which may be due to reduced availability of peptides in the ER as a result of TAP inhibition. Metabolic inhibition studies indicated that an early protein(s) of EHV-1 is responsible for this effect.
Ambagala
Aruna P N
APN
Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, NE 68583-0905, USA.
Gopinath
Raju S
RS
Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, NE 68583-0905, USA.
Srikumaran
S
S
Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, NE 68583-0905, USA.
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001693:Biological Transport, Active; D002460:Cell Line; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004861:Herpesvirus 1, Equid / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000378:metabolism*; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D049990:Membrane Transport Modulators; D026901:Membrane Transport Proteins; C477327:transporter associated with antigen processing (TAP); C043912:peptide permease