The late lytic LMP-1 protein of Epstein-Barr virus can negatively regulate LMP-1 signaling.
The BNLF-1 open reading frame of Epstein-Barr virus (EBV) encodes two related proteins, latent membrane protein-1 (LMP-1) and lytic LMP-1 (lyLMP-1). LMP-1 is a latent protein required for immortalization of human B cells by EBV, whereas lyLMP-1 is expressed during the lytic cycle and is found in the EBV virion. We show here that, in contrast to LMP-1, lyLMP-1 is stable, with a half-life of >20 h in tetradecanoyl phorbol acetate- and butyrate-treated B95-8 cells. Although lyLMP-1 itself has negligible effects on NF-kappaB activity, it inhibits NF-kappaB activation by LMP-1 in a dose-dependent manner. The lyLMP-1 protein does not oligomerize with LMP-1, and the negative effect of lyLMP-1 on NF-kappaB activation by LMP-1 does not result from lyLMP-1-mediated disruption of LMP-1 oligomers. Modulation of LMP-1-activated signaling pathways is the first identified biological activity associated with lyLMP-1, and this activity may contribute to the progression of EBV's lytic cycle.
Erickson
K D
KD
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA.
Martin
J M
JM
D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D002461:Cell Line, Transformed; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000378:metabolism*
D002087:Butyrates; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins; D013755:Tetradecanoylphorbol Acetate