title: SARS-CoV accessory protein 3b induces AP-1 transcriptional activity through activation of JNK and ERK pathways.
abstract: The outbreak of severe acute respiratory syndrome (SARS) in 2003 in China, characterized by atypical pneumonia, was associated with the emergence of a novel coronavirus named severe acute respiratory syndrome coronavirus (SARS-CoV). Eight accessory proteins of SARS coronavirus were the suspected players in the pathogenesis of the virus. Among them, protein 3b localizes to the nucleus and behaves as an interferon antagonist by inhibiting IRF3 activation. However, the effect of 3b on the activity of other common host transcription factors remains unexplored. In this work, we studied the effect of 3b on the transcriptional activity of AP-1. Our findings elucidate augmentation of AP-1-dependent gene expression in 3b-transfected Huh7 cells. Reporter gene and mobility shift assays depict an increase in the AP-1 transcriptional and DNA binding activity in the presence of 3b. This increase in activity correlates with the activation of ERK and JNK pathways. Furthermore, 3b expression potentiates AP-1-driven promoter activity of proinflammatory cytokine MCP-1, suggesting a plausible role for 3b as a virulence factor that might function by upregulating AP-1-dependent cytokine levels in SARS-CoV infection.
authors.affiliation: Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110018, India.
authors.forename: Bhavna
authors.initials: B
authors.lastname: Varshney
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Lal
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics; D002522:Chlorocebus aethiops; D015342:DNA Probes / Q000235:genetics; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D014709:Vero Cells; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015342:DNA Probes; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D054334:Viral Regulatory and Accessory Proteins; D048031:JNK Mitogen-Activated Protein Kinases