The bZip dimerization domain of the Epstein-Barr virus BZLF1 (Z) protein mediates lymphoid-specific negative regulation.
The Epstein-Barr virus (EBV) immediate-early (IE) protein, BZLF1 (Z), initiates the switch from latent to lytic infection, Z transactivation of an early viral promoter, BMRF1, is relatively inefficient in lymphoid cells (compared with epithelial cells), unless the other EBV IE protein, BRLF1, is also present. Cellular proteins, including the p65 component of NF-kappa B, have been shown to interact directly with Z in vitro through the bZip dimerization domain and inhibit Z-induced transactivation. Here we precisely define a residue within the bZip dimerization domain of Z (amino acid 200) which is required for interaction in vitro with the p65 component of NF-kappa B, but is not essential for Z homodimerization. In lymphoid cells, a Z mutant which has been altered at amino acid 200 (tyrosine to glutamic acid) transactivates both the early BMRF1 promoter and the immediate-early BZLF1 promoter (Zp) four- to fivefold better than wild-type Z. In contrast, mutation of amino acid 200 does not affect Z transactivator function in epithelial cells. The results suggest that Z function is specifically inhibited by a lymphoid-specific protein(s) through amino acid 200 in the bZip dimerization domain. Modulation of Z's activator function may help to regulate the stringency of viral latency in lymphocytes.
Hong
Y
Y
Department of Medicine, Lineberger Comprehensive-Cancer Center, University of North Carolina at Chapel Hill 27599, USA.
Holley-Guthrie
E
E
Kenney
S
S
D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000502:physiology*; D011485:Protein Binding; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014764:Viral Proteins; D017735:Virus Latency
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D015534:Trans-Activators; D014764:Viral Proteins