Inhibition of MHC class I-restricted antigen presentation by gamma 2-herpesviruses.
The gamma-herpesviruses, in contrast to the alpha- and beta-herpesviruses, are not known to inhibit antigen presentation to CD8(+) cytotoxic T lymphocytes (CTLs) during lytic cycle replication. However, murine gamma-herpesvirus 68 causes a chronic lytic infection in CD4(+) T cell-deficient mice despite the persistence of a substantial CTL response, suggesting that CTL evasion occurs. Here we show that, distinct from host protein synthesis shutoff, gamma-herpesvirus 68 down-regulates surface MHC class I expression on lytically infected fibroblasts and inhibits their recognition by antigen-specific CTLs. The viral K3 gene, encoding a zinc-finger-containing protein, dramatically reduced the half-life of nascent class I molecules and the level of surface MHC class I expression and was by itself sufficient to block antigen presentation. The homologous K3 and K5 genes of the related Kaposi's sarcoma-associated virus also inhibited antigen presentation and decreased cell surface expression of HLA class I antigens. Thus it appears that an immune evasion strategy shared by at least two gamma-herpesviruses allows continued lytic infection in the face of strong CTL immunity.
Stevenson
P G
PG
Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom. pgs27@mole.bio.cam.ac.uk
Efstathiou
S
S
Doherty
P C
PC
Lehner
P J
PJ
D016475:3T3 Cells; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002461:Cell Line, Transformed; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004285:Dogs; D018142:Gammaherpesvirinae / Q000276:immunology*; D005814:Genes, Viral; D006183:H-2 Antigens / Q000096:biosynthesis / Q000276:immunology*; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D006825:Hybridomas; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology
D000956:Antigens, Viral; D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D