STAT1 contributes to the maintenance of the latency III viral programme observed in Epstein-Barr virus-transformed B cells and their recognition by CD8+ T cells

• Published in: Journal of general virology Vol. 90; no. 9; pp. 2239 - 2250
• Main Authors: McLaren, James E, Zuo, Jianmin, Grimstead, Julia, Poghosyan, Zara, Bell, Andrew I, Rowe, Martin, Brennan, Paul
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.09.2009; Society for General Microbiology
• Subjects: Antigen processing; B-Lymphocytes - immunology; B-Lymphocytes - virology; Biological and medical sciences; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Line, Transformed; Cell surface; Cell Transformation, Viral; Epstein-Barr virus; Epstein-Barr Virus Infections - genetics; Epstein-Barr Virus Infections - immunology; Epstein-Barr Virus Infections - virology; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene transfer; Herpesvirus 4, Human - immunology; Herpesvirus 4, Human - physiology; Humans; Immunosurveillance; Interferon; LMP2A protein; Lymphoblastoid cell lines; Lymphocytes B; Lymphocytes T; Major histocompatibility complex; Microbiology; Miscellaneous; Molecular modelling; proteasomes; Signal transduction; Simian virus 5; Stat1 protein; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - immunology; Transcription factors; Transformation; Viral Structural Proteins - genetics; Viral Structural Proteins - immunology; Virology; Virus Latency; Gammaherpesvirinae; Virus; Microbiology; Herpesviridae; T-Lymphocyte; B-Lymphocyte; Epstein Barr virus; Recognition
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.011627-0

1 Department of Medical Biochemistry and Immunology, Henry Wellcome Research Institute, Cardiff University, Heath Park, Cardiff CF14 4XN, UK 2 Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK 3 Department of Pathology, Henry Wellcome Research Institute, Cardiff University, Heath Park, Cardiff CF14 4XN, UK Correspondence James E. McLaren mclarenje{at}cf.ac.uk The transformation of B cells by Epstein–Barr virus (EBV), into lymphoblastoid cell lines (LCLs) results in the upregulation of STAT1, a key transcription factor in the interferon signalling pathway. Although the mechanism of EBV induction of STAT1 protein expression has been intensively studied, there has been little investigation into the function of STAT1 in EBV-transformed LCLs. In this study, we have implemented a novel strategy to investigate the functional role of STAT1 through the introduction of the simian virus 5 (SV5) V-protein into LCLs by retroviral gene transfer. The V-protein is a virally evolved STAT1 inhibitor that specifically targets STAT1 for proteasomal degradation. Using this in vitro model, we have shown that major histocompatibility complex (MHC) class I and class II molecules are downregulated at the cell surface following a reduction in STAT1 protein expression. With regards to MHC class I, the impairment of the antigen processing machinery renders the cells less recognized by the host EBV-specific immunosurveillance. In addition, downregulation of STAT1 increases the expression of LMP2A and lytic cycle antigens and results in a higher proportion of cells entering the lytic cycle. These results suggest that STAT1 is involved in maintaining the latency III viral program observed in transformed B cells and regulating immunorecognition by EBV-specific T cells.