Multiple Bcl-2 family immunomodulators from vaccinia virus regulate MAPK/AP-1 activation.
Vaccinia virus (VACV) is a poxvirus and encodes many proteins that modify the host cell metabolism or inhibit the host response to infection. For instance, it is known that VACV infection can activate the mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) pathway and inhibit activation of the pro-inflammatory transcription factor NF-κB. Since NF-κB and MAPK/AP-1 share common upstream activators we investigated whether six different VACV Bcl-2-like NF-κB inhibitors can also influence MAPK/AP-1 activation. Data presented show that proteins A52, B14 and K7 each contribute to AP-1 activation during VACV infection, and when expressed individually outwith infection. B14 induced the greatest stimulation of AP-1 and further investigation showed B14 activated mainly the MAPKs ERK (extracellular signal-regulated kinase) and JNK (Jun N-terminal kinase), and their substrate c-Jun (a component of AP-1). These data indicate that the same viral protein can have different effects on distinct signalling pathways, in blocking NF-κB activation whilst leading to MAPK/AP-1 activation.
Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, MG, Brazil.|Department of Pathology, University of Cambridge, Cambridge, UK.
Alice A
AA
Torres
Department of Pathology, University of Cambridge, Cambridge, UK.
Jonas D
JD
Albarnaz
Laboratório de Vírus, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, MG, Brazil.
Cláudio A
CA
Bonjardim
Department of Pathology, University of Cambridge, Cambridge, UK.
Geoffrey L
GL
Smith
D054884:Host-Pathogen Interactions; D007155:Immunologic Factors / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014616:Vaccinia virus / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism*
D007155:Immunologic Factors; D018808:Transcription Factor AP-1; D014764:Viral Proteins