NF-kappaB only partially mediates Epstein-Barr virus latent membrane protein 1 activation of B cells.
The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is required for EBV-induced immortalization of human B cells and causes tumorigenic transformation of cell lines. LMP1 expression induces phenotypic changes resembling B cell activation, such as cell size increase and up-regulation of cell surface activation markers. LMP1 contains two domains that activate the transcription factor NF-kappaB, one through interactions with TRAF proteins and the other with the TRADD protein. The purpose of the present study was to investigate the importance of NF-kappaB induction in the up-regulation of the B cell activation markers ICAM-1 and CD71 by LMP1. This study shows that expression of LMP1 activates transcription from p50/p65- and c-Rel-responsive promoters, and that this activity can be completely inhibited by expression of a dominant inhibitory IkappaB mutant. ICAM-1 and CD71 are nevertheless up-regulated by LMP1 in primary B cells and cell lines expressing the dominant IkappaB. Furthermore, LMP1-induced cell size increase of primary B cells was unaffected by IkappaB expression. It was concluded that even when LMP1 is unable to activate NF-kappaB, it is still capable of inducing certain characteristics of activated B cells, strongly suggesting that LMP1 can also activate cells independently of NF-kappaB.
Liljeholm
S
S
Department of Cell and Molecular Biology, Umeå University, Sweden.
Hughes
K
K
Grundström
T
T
Brodin
P
P
D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D020672:I-kappa B Proteins; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008213:Lymphocyte Activation; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011990:Receptors, Transferrin / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011990:Receptors, Transferrin; D014763:Viral Matrix Proteins; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha