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Rescue of the Epstein-Barr virus BZLF1 mutant, Z(S186A), early gene activation defect by the BRLF1 gene product.
Virology. 1998 Nov 10; 251(1):187-97.V

Abstract

Expression of the Epstein-Barr virus (EBV) immediate-early protein, BZLF1 (Z), is sufficient to disrupt viral latency. Z transcriptionally activates the EBV early genes by binding to upstream Z-responsive elements (ZREs). Recently, a serine-to-alanine mutation of Z residue 186 (within the basic DNA binding domain) was shown to inhibit the ability of Z to induce lytic infection in latently infected cells, although the Z(S186A) mutant could still bind several known ZREs and activated an early EBV promoter (BMRF1) in transient reporter gene assays (Francis, A. L., Gradoville, L., and Miller, G. (1997). J. Virol. 71, 3054-3061). We now show that a specific deficiency in the ability to bind to ZRE elements in the immediate-early BRLF1 promoter may account for the inability of Z(S186A) to activate BRLF1 expression. Furthermore, we demonstrate that the ability of Z(S186A) to induce early BMRF1 and BHRF1 gene expression is rescued by cotransfection with a BRLF1 expression vector. However, the Z(S186A)/BRLF1 (R) combination cannot induce full lytic replication, suggesting that Z(S186A) may also be deficient in a replication-specific function. These results suggest that in the context of the intact viral genome, both Z and R expression are required for activation of early gene transcription in latently infected cells.

Authors+Show Affiliations

Lineberger Comprehensive Cancer Center, Departments of Medicine and Microbiology, University of North Carolina at Chapel Hill, North Carolina, Chapel Hill, 27599-7295, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9813214

Citation

Adamson, A L., and S C. Kenney. "Rescue of the Epstein-Barr Virus BZLF1 Mutant, Z(S186A), Early Gene Activation Defect By the BRLF1 Gene Product." Virology, vol. 251, no. 1, 1998, pp. 187-97.
Adamson AL, Kenney SC. Rescue of the Epstein-Barr virus BZLF1 mutant, Z(S186A), early gene activation defect by the BRLF1 gene product. Virology. 1998;251(1):187-97.
Adamson, A. L., & Kenney, S. C. (1998). Rescue of the Epstein-Barr virus BZLF1 mutant, Z(S186A), early gene activation defect by the BRLF1 gene product. Virology, 251(1), 187-97.
Adamson AL, Kenney SC. Rescue of the Epstein-Barr Virus BZLF1 Mutant, Z(S186A), Early Gene Activation Defect By the BRLF1 Gene Product. Virology. 1998 Nov 10;251(1):187-97. PubMed PMID: 9813214.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rescue of the Epstein-Barr virus BZLF1 mutant, Z(S186A), early gene activation defect by the BRLF1 gene product. AU - Adamson,A L, AU - Kenney,S C, PY - 1998/11/14/pubmed PY - 1998/11/14/medline PY - 1998/11/14/entrez SP - 187 EP - 97 JF - Virology JO - Virology VL - 251 IS - 1 N2 - Expression of the Epstein-Barr virus (EBV) immediate-early protein, BZLF1 (Z), is sufficient to disrupt viral latency. Z transcriptionally activates the EBV early genes by binding to upstream Z-responsive elements (ZREs). Recently, a serine-to-alanine mutation of Z residue 186 (within the basic DNA binding domain) was shown to inhibit the ability of Z to induce lytic infection in latently infected cells, although the Z(S186A) mutant could still bind several known ZREs and activated an early EBV promoter (BMRF1) in transient reporter gene assays (Francis, A. L., Gradoville, L., and Miller, G. (1997). J. Virol. 71, 3054-3061). We now show that a specific deficiency in the ability to bind to ZRE elements in the immediate-early BRLF1 promoter may account for the inability of Z(S186A) to activate BRLF1 expression. Furthermore, we demonstrate that the ability of Z(S186A) to induce early BMRF1 and BHRF1 gene expression is rescued by cotransfection with a BRLF1 expression vector. However, the Z(S186A)/BRLF1 (R) combination cannot induce full lytic replication, suggesting that Z(S186A) may also be deficient in a replication-specific function. These results suggest that in the context of the intact viral genome, both Z and R expression are required for activation of early gene transcription in latently infected cells. SN - 0042-6822 UR - https://www.unboundmedicine.com/medline/citation/9813214/Rescue_of_the_Epstein_Barr_virus_BZLF1_mutant_Z_S186A__early_gene_activation_defect_by_the_BRLF1_gene_product_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0042-6822(98)99396-5 DB - PRIME DP - Unbound Medicine ER -