Induction of interferon-stimulated genes by Simian virus 40 T antigens.
Simian virus 40 (SV40) large T antigen (TAg) is a multifunctional oncoprotein essential for productive viral infection and for cellular transformation. We have used microarray analysis to examine the global changes in cellular gene expression induced by wild-type T antigen (TAg(wt)) and TAg-mutants in mouse embryo fibroblasts (MEFs). The expression profile of approximately 800 cellular genes was altered by TAg(wt) and a truncated TAg (TAg(N136)), including many genes that influence cell cycle, DNA-replication, transcription, chromatin structure and DNA repair. Unexpectedly, we found a significant number of immune response genes upregulated by TAg(wt) including many interferon-stimulated genes (ISGs) such as ISG56, OAS, Rsad2, Ifi27 and Mx1. Additionally, we also observed activation of STAT1 by TAg(wt). Our genetic studies using several TAg-mutants reveal an unexplored function of TAg and indicate that the LXCXE motif and p53 binding are required for the upregulation of ISGs.
Rathi
Abhilasha V
AV
Department of Biological Sciences, University of Pittsburgh, 559 Crawford Hall, Pittsburgh, PA 15260, USA.
Cantalupo
Paul G
PG
Sarkar
Saumendra N
SN
Pipas
James M
JM
D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology; D005786:Gene Expression Regulation; D007372:Interferons / Q000235:genetics / Q000276:immunology*; D051379:Mice; D027601:Polyomavirus Infections / Q000235:genetics* / Q000276:immunology; D013539:Simian virus 40 / Q000235:genetics / Q000276:immunology*; D014412:Tumor Virus Infections / Q000235:genetics* / Q000276:immunology
D000957:Antigens, Viral, Tumor; D007372:Interferons