African swine fever virus IAP-like protein induces the activation of nuclear factor kappa B.
African swine fever virus (ASFV) encodes a homologue of the inhibitor of apoptosis (IAP) that promotes cell survival by controlling the activity of caspase-3. Here we show that ASFV IAP is also able to activate the transcription factor NF-kappaB. Thus, transient transfection of the viral IAP increases the activity of an NF-kappaB reporter gene in a dose-responsive manner in Jurkat cells. Similarly, stably transfected cells expressing ASFV IAP have elevated basal levels of c-rel, an NF-kappaB-dependent gene. NF-kappaB complexes in the nucleus were increased in A224L-expressing cells compared with control cells upon stimulation with phorbol myristate acetate (PMA) plus ionomycin. This resulted in greater NF-kappaB-dependent promoter activity in ASFV IAP-expressing than in control cells, both in basal conditions and after PMA plus ionophore stimulation. The elevated NF-kappaB activity seems to be the consequence of higher IkappaB kinase (IKK) basal activity in these cells. The NF-kappaB-inducing activity of ASFV IAP was abrogated by an IKK-2 dominant negative mutant and enhanced by expression of tumor necrosis factor receptor-associated factor 2.
Rodríguez
Clara I
CI
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain.
Nogal
María L
ML
Carrascosa
Angel L
AL
Salas
María L
ML
Fresno
Manuel
M
Revilla
Yolanda
Y
D000358:African Swine Fever Virus / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D016328:NF-kappa B / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2; D014162:Transfection
D020672:I-kappa B Proteins; D051034:Inhibitor of Apoptosis Proteins; D019476:Insect Proteins; D016328:NF-kappa B; D011506:Proteins; D047992:TNF Receptor-Associated Factor 2