The latent membrane protein 1 of Epstein-Barr virus (EBV) primes EBV latency cells for type I interferon production.
Epstein-Barr virus (EBV) latency has been associated with a variety of human cancers. Latent membrane protein 1 (LMP-1) is one of the key viral proteins required for transformation of primary B cells in vitro and establishment of EBV latency. We have previously shown that LMP-1 induces the expression of several interferon (IFN)-stimulated genes and has antiviral effect (Zhang, J., Das, S. C., Kotalik, C., Pattnaik, A. K., and Zhang, L. (2004) J. Biol. Chem. 279, 46335-46342). In this report, a novel mechanism related to the antiviral effect of LMP-1 is identified. We show that EBV type III latency cells, in which LMP-1 is expressed, are primed to produce robust levels of endogenous IFNs upon infection of Sendai virus. The priming action is due to the expression of LMP-1 but not EBV nuclear antigen 2 (EBNA-2). The signaling events from the C-terminal activator regions of LMP-1 are essential to prime cells for high IFN production. LMP-1-mediated activation of NF-kappaB is apparently necessary and sufficient for LMP-1-mediated priming effect in DG75 cells, a human B cell line. IFN regulatory factor 7 (IRF-7) that can be activated by LMP-1 is also implicated in the priming action. Taken together, these data strongly suggest that LMP-1 may prime EBV latency cells for IFN production and that the antiviral property of LMP-1 may be an intrinsic part of EBV latency program, which may assist the establishment and/or maintenance of viral latency.
Nebraska Center for Virology.
Dongsheng
D
Xu
Kristen
K
Brumm
Luwen
L
Zhang
D002051:Burkitt Lymphoma; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000502:physiology; D007370:Interferon Type I / Q000096:biosynthesis*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000502:physiology*; D017735:Virus Latency
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D050839:Interferon Regulatory Factor-7; D007370:Interferon Type I; D014763:Viral Matrix Proteins