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Inhibition of heavy chain and beta2-microglobulin synthesis as a mechanism of major histocompatibility complex class I downregulation during Epstein-Barr virus replication.
- Source :
-
Journal of virology [J Virol] 2007 Feb; Vol. 81 (3), pp. 1390-400. Date of Electronic Publication: 2006 Nov 15. - Publication Year :
- 2007
-
Abstract
- The mechanisms of major histocompatibility complex (MHC) class I downregulation during Epstein-Barr virus (EBV) replication are not well characterized. Here we show that in several cell lines infected with a recombinant EBV strain encoding green fluorescent protein (GFP), the virus lytic cycle coincides with GFP expression, which thus can be used as a marker of virus replication. EBV replication resulted in downregulation of MHC class II and all classical MHC class I alleles independently of viral DNA synthesis or late gene expression. Although assembled MHC class I complexes, the total pool of heavy chains, and beta2-microglobulin (beta2m) were significantly downregulated, free class I heavy chains were stabilized at the surface of cells replicating EBV. Calnexin expression was increased in GFP+ cells, and calnexin and calreticulin accumulated at the cell surface that could contribute to the stabilization of class I heavy chains. Decreased expression levels of another chaperone, ERp57, and TAP2, a transporter associated with antigen processing and presentation, correlated with delayed kinetics of MHC class I maturation. Levels of both class I heavy chain and beta2m mRNA were reduced, and metabolic labeling experiments demonstrated a very low rate of class I heavy chain synthesis in lytically infected cells. MHC class I and MHC class II downregulation was mimicked by pharmacological inhibition of protein synthesis in latently infected cells. Our data suggest that although several mechanisms may contribute to MHC class I downregulation in the course of EBV replication, inhibition of MHC class I synthesis plays the primary role in the process.
- Subjects :
- Cell Line, Transformed
Down-Regulation
Genes, Immunoglobulin Heavy Chain
Herpesvirus 4, Human immunology
Humans
beta 2-Microglobulin genetics
beta 2-Microglobulin metabolism
Herpesvirus 4, Human physiology
Histocompatibility Antigens Class I physiology
Virus Replication physiology
beta 2-Microglobulin chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0022-538X
- Volume :
- 81
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 17108039
- Full Text :
- https://doi.org/10.1128/JVI.01999-06