Pseudorabies virus US3- and UL49.5-dependent and -independent downregulation of MHC I cell surface expression in different cell types.
Many herpesviruses interfere with the MHC I antigen-processing pathway in order to limit elimination by cytotoxic T-lymphocytes. For varicelloviruses, the largest subgroup of alphaherpesviruses, two viral proteins have been reported to downregulate MHC I cell surface expression: UL49.5 for BoHV-1, PRV, and EHV-1 and the US3 orthologue for VZV. Here, we report that PRV reduces MHC I cell surface expression during infection in a cell-type-dependent manner. In ST cells, a kinase-active US3 was necessary but not sufficient to downregulate cell surface MHC I expression, whereas US3 was not required in PK-15 cells and porcine alveolar macrophages (PAM). MHC I downregulation was not (PAM, ST) or only partly (PK-15) dependent on UL49.5. In conclusion, we show that the mechanism(s) of PRV-mediated cell surface MHC I downregulation are cell-type-dependent, with variable roles for US3, UL49.5, and additional, yet unidentified early viral proteins.
Deruelle
Matthias J
MJ
Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium. Matthias.Deruelle@UGent.be
Van den Broeke
Céline
C
Nauwynck
Hans J
HJ
Mettenleiter
Thomas C
TC
Favoreel
Herman W
HW
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D005805:Genes, MHC Class I / Q000235:genetics / Q000502:physiology*; D011558:Herpesvirus 1, Suid / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D013737:Testis / Q000166:cytology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D008565:Membrane Proteins; D020033:Protein Isoforms; D014764:Viral Proteins