Inactivation of NF-kappaB by EBV BZLF-1-encoded ZEBRA protein in human T cells.
We have previously shown that the EBV ZEBRA protein (also denoted EB1, Z, or Zta) encoded by the BZLF open reading frame is expressed in primary human thymocytes and in human T lymphoblastoid cell lines infected by EBV. Expression of EBV-encoded gene products in T lymphocytes could contribute to viral pathogenesis during acute EBV infection as well as in individuals coinfected with EBV and HIV. HPB-ALL and Jurkat T lymphoblastoid cell lines transiently and stably expressing ZEBRA were characterized in this work. Expression of ZEBRA protein in human T lymphoblastoid cells was associated with decreased expression of an NF-kappaB reporter gene, altered expression of the NF-kappaB p50 protein subunit, and decreased DNA binding by components of NF-kappaB. These observations suggest that inactivation of NF-kappaB transcription by ZEBRA in EBV-infected T cells may be a novel mechanism of viral pathogenesis analogous in part to over-expression of the endogenous cytoplasmic inhibitor of NF-kappaB, IkappaBalpha.
Dreyfus
D H
DH
Division of Basic Sciences, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Nagasawa
M
M
Pratt
J C
JC
Kelleher
C A
CA
Gelfand
E W
EW
D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D015534:Trans-Activators; D014764:Viral Proteins