sars coronavirus 3b accessory protein modulates transcriptional activity of runx1bsars冠状病毒3 b runx1b附属蛋白调节转录活动.pdfVIP

SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b 1 2 3 2 1 Bhavna Varshney , Sudhakar Agnihotram , Yee-Joo Tan , Ralph Baric , Sunil K. Lal * 1Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India, 2 Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States of America, 3 Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore Abstract Background: The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. Methodology/Principal Findings: In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcrip