Identification of a novel element involved in regulation of the lytic switch BZLF1 gene promoter of Epstein-Barr virus.

Abstract:

:Epstein-Barr virus (EBV) is a human herpesvirus capable of establishing a latent state in B lymphocytes. EBV's BZLF1 gene product plays a central role in regulating the switch from latency to productive infection. Here, we identify a sequence element, 5'-CAGGTA-3', called ZV, located at nucleotides -17 to -12 relative to the transcription initiation site of the BZLF1 promoter. ZV sequence-specifically binds a cellular nuclear factor(s), ZVR. ZVR DNA-binding activity was present in the EBV-negative B-lymphocytic cell line DG75, the EBV-positive B-lymphocytic cell lines GG68 and 721, the cervical cell line C33A, and the kidney cell line CV-1 but not in the breast carcinoma cell line MCF-7. Mutations in ZV that relieve binding of ZVR lead to a two- to fourfold increase in basal expression of the BZLF1 promoter in DG75, C33A, and CV-1 cells. The same mutants exhibited a 40- to 180-fold increase in tetradecanoyl phorbol acetate-ionomycin-induced expression in DG75 cells and a 22-fold increase in C33A cells. Thus, ZVR functions as a regulator of the BZLF1 promoter, repressing transcription when bound to the ZV site in the absence of inducers. No differences in basal or induced transcription between wild-type and ZV mutant BZLF1 promoters were observed in ZVR-negative MCF-7 cells. ZVR failed to bind any of the previously identified negative regulatory elements within the BZLF1 promoter. We conclude that ZV functions as an important regulatory element of the BZLF1 promoter, with ZVR likely playing important roles in the maintenance of latency and reactivation of EBV.

journal_name

J Virol

journal_title

Journal of virology

authors

Kraus RJ,Mirocha SJ,Stephany HM,Puchalski JR,Mertz JE

doi

10.1128/JVI.75.2.867-877.2001

subject

Has Abstract

pub_date

2001-01-01 00:00:00

pages

867-77

issue

2

eissn

0022-538X

issn

1098-5514

journal_volume

75

pub_type

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