Abstract
The Epstein-Barr virus (EBV) BMRF1 protein is a DNA polymerase processivity factor. We have deleted the BMRF1 open reading frame from the EBV genome and assessed the DeltaBMRF1 EBV phenotype. DeltaBMRF1 viruses were replication deficient, but the wild-type phenotype could be restored by BMRF1 trans-complementation. The replication-deficient phenotype included impaired lytic DNA replication and late protein expression. DeltaBMRF1 and wild-type viruses were undistinguishable in terms of their ability to transform primary B cells. Our results provide genetic evidence that BMRF1 is essential for lytic replication of the EBV genome.
MeSH Terms
Antigens, Viral/genetics,physiology
B-Lymphocytes/metabolism,pathology
Cell Transformation, Neoplastic/genetics,pathology
Cell Transformation, Viral/genetics
DNA Replication/genetics
Gene Deletion
Genome, Viral
Herpesvirus 4, Human/genetics
Humans
Virus Replication/genetics
Chemicals
Antigens, Viral
Epstein-Barr virus early antigen diffuse component
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Neuhierl Bernhard
German Cancer Research Center, Department of Virus Associated Tumours, Im Neuenheimer Feld 242, 69120 Heidelberg, Germany.
Delecluse Henri-Jacques
References (25)
25 references, click to expand
-
Functional interaction between Epstein-Barr virus DNA polymerase catalytic subunit and its accessory subunit in vitro.
J Virol. 1993 Dec;67(12):7648-53
PMID: 8230484
-
Propagation and recovery of intact, infectious Epstein-Barr virus from prokaryotic to human cells.
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8245-50
PMID: 9653172
-
The Epstein-Barr virus (EBV) DNA polymerase accessory protein, BMRF1, activates the essential downstream component of the EBV oriLyt.
Virology. 1997 Mar 31;230(1):22-34
PMID: 9126259
-
Proteins of purified Epstein-Barr virus.
Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16286-91
PMID: 15534216
-
Detecting the ability of viral, bacterial and eukaryotic replication proteins to track along DNA.
EMBO J. 1994 Nov 15;13(22):5330-7
PMID: 7957099
-
The cellular oncogene c-myb can interact synergistically with the Epstein-Barr virus BZLF1 transactivator in lymphoid cells.
Mol Cell Biol. 1992 Jan;12(1):136-46
PMID: 1309587
-
Architecture of replication compartments formed during Epstein-Barr virus lytic replication.
J Virol. 2005 Mar;79(6):3409-18
PMID: 15731235
-
Characteristics of a human cell line transformed by DNA from human adenovirus type 5.
J Gen Virol. 1977 Jul;36(1):59-74
PMID: 886304
-
trans-acting requirements for replication of Epstein-Barr virus ori-Lyt.
J Virol. 1992 Aug;66(8):5030-9
PMID: 1321285
-
Purification and characterization of the DNA-binding activity of the Epstein-Barr virus DNA polymerase accessory protein BMRF1 gene products, as expressed in insect cells by using the baculovirus system.
J Virol. 1993 Mar;67(3):1681-7
PMID: 8382315
-
Functional and physical interactions between the Epstein-Barr virus (EBV) proteins BZLF1 and BMRF1: Effects on EBV transcription and lytic replication.
J Virol. 1996 Aug;70(8):5131-42
PMID: 8764021
-
CYTOLOGY OF BURKITT'S TUMOUR (AFRICAN LYMPHOMA).
Lancet. 1964 Feb 1;1(7327):238-40
PMID: 14086209
-
Identification of polypeptide components of the Epstein-Barr virus early antigen complex with monoclonal antibodies.
J Virol. 1983 Jul;47(1):193-201
PMID: 6306272
-
Early events in Epstein-Barr virus genome expression after activation: regulation by second messengers of B cell activation.
Virology. 1991 Dec;185(2):922-8
PMID: 1660209
-
Isolation of a herpes simplex virus type 1 mutant deleted for the essential UL42 gene and characterization of its null phenotype.
J Virol. 1991 Feb;65(2):700-10
PMID: 1846193
-
The regulated expression of Epstein-Barr virus. III. Proteins specified by EBV during the lytic cycle.
J Gen Virol. 1981 Sep;56(Pt 1):105-18
PMID: 6271909
-
Molecular genetics of DNA viruses: recombinant virus technology.
Methods Mol Biol. 2005;292:353-70
PMID: 15507720
-
Identification of herpes simplex virus type 1 genes required for origin-dependent DNA synthesis.
J Virol. 1988 Feb;62(2):435-43
PMID: 2826806
-
One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products.
Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6640-5
PMID: 10829079
-
Mechanism of the sliding beta-clamp of DNA polymerase III holoenzyme.
J Biol Chem. 1991 Jun 15;266(17):11328-34
PMID: 2040637
-
Cooperation of EBV DNA polymerase and EA-D(BMRF1) in vitro and colocalization in nuclei of infected cells.
Virology. 1991 Sep;184(1):330-40
PMID: 1651595
-
Latent Marek's disease virus can be activated from its chromosomally integrated state in herpesvirus-transformed lymphoma cells.
EMBO J. 1993 Aug;12(8):3277-86
PMID: 8393785
-
The Epstein-Barr virus protein BMRF1 activates gastrin transcription.
J Virol. 2005 Jan;79(2):745-55
PMID: 15613302
-
Detection of circular and linear herpesvirus DNA molecules in mammalian cells by gel electrophoresis.
J Virol. 1984 Apr;50(1):248-54
PMID: 6321792
-
Herpes simplex virus processivity factor UL42 imparts increased DNA-binding specificity to the viral DNA polymerase and decreased dissociation from primer-template without reducing the elongation rate.
J Virol. 1999 Jan;73(1):55-66
PMID: 9847307