Abstract
We have identified conserved autoantigenic cellular proteins that bind to G-rich sequence motifs in recombinogenic regions of Epstein-Barr virus (EBV) DNA. This binding activity, called TRBP, recognizes the EBV terminal repeats, a locus responsible for interconversion of linear and circular EBV DNA. We found that TRBP also binds to EBV DNA sequences involved in deletion of EBNA2, a gene product required for immortalization. We show that TRBP binds sequences present in repetitive cellular DNA, such as variable-number tandem repeats (VNTR) and immunoglobulin heavy-chain class switch regions. We propose that EBV utilizes cellular DNA recombination systems to mediate several types of viral genome alterations. These findings may lead to an understanding of the mechanism of rearrangements of EBV DNA that are a central feature of the biology of the virus.
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- Adams A., Lindahl T. Epstein-Barr virus genomes with properties of circular DNA molecules in carrier cells. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1477–1481. doi: 10.1073/pnas.72.4.1477. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Allan G. J., Rowe D. T. Size and stability of the Epstein-Barr virus major internal repeat (IR-1) in Burkitt's lymphoma and lymphoblastoid cell lines. Virology. 1989 Dec;173(2):489–498. doi: 10.1016/0042-6822(89)90561-8. [DOI] [PubMed] [Google Scholar]
- Andersson J., Coutinho A., Lernhardt W., Melchers F. Clonal growth and maturation to immunoglobulin secretion in vitro of every growth-inducible B lymphocyte. Cell. 1977 Jan;10(1):27–34. doi: 10.1016/0092-8674(77)90136-2. [DOI] [PubMed] [Google Scholar]
- Baer R., Bankier A. T., Biggin M. D., Deininger P. L., Farrell P. J., Gibson T. J., Hatfull G., Hudson G. S., Satchwell S. C., Séguin C. DNA sequence and expression of the B95-8 Epstein-Barr virus genome. Nature. 1984 Jul 19;310(5974):207–211. doi: 10.1038/310207a0. [DOI] [PubMed] [Google Scholar]
- Bornkamm G. W., Hudewentz J., Freese U. K., Zimber U. Deletion of the nontransforming Epstein-Barr virus strain P3HR-1 causes fusion of the large internal repeat to the DSL region. J Virol. 1982 Sep;43(3):952–968. doi: 10.1128/jvi.43.3.952-968.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gardella T., Medveczky P., Sairenji T., Mulder C. Detection of circular and linear herpesvirus DNA molecules in mammalian cells by gel electrophoresis. J Virol. 1984 Apr;50(1):248–254. doi: 10.1128/jvi.50.1.248-254.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hammerschmidt W., Sugden B. Identification and characterization of oriLyt, a lytic origin of DNA replication of Epstein-Barr virus. Cell. 1988 Nov 4;55(3):427–433. doi: 10.1016/0092-8674(88)90028-1. [DOI] [PubMed] [Google Scholar]
- Hurley E. A., Agger S., McNeil J. A., Lawrence J. B., Calendar A., Lenoir G., Thorley-Lawson D. A. When Epstein-Barr virus persistently infects B-cell lines, it frequently integrates. J Virol. 1991 Mar;65(3):1245–1254. doi: 10.1128/jvi.65.3.1245-1254.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jeang K. T., Hayward S. D. Organization of the Epstein-Barr virus DNA molecule. III. Location of the P3HR-1 deletion junction and characterization of the NotI repeat units that form part of the template for an abundant 12-O-tetradecanoylphorbol-13-acetate-induced mRNA transcript. J Virol. 1983 Oct;48(1):135–148. doi: 10.1128/jvi.48.1.135-148.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jeffreys A. J., Wilson V., Thein S. L. Hypervariable 'minisatellite' regions in human DNA. Nature. 1985 Mar 7;314(6006):67–73. doi: 10.1038/314067a0. [DOI] [PubMed] [Google Scholar]
- Jenson H. B., Farrell P. J., Miller G. Sequences of the Epstein-Barr Virus (EBV) large internal repeat form the center of a 16-kilobase-pair palindrome of EBV (P3HR-1) heterogeneous DNA. J Virol. 1987 May;61(5):1495–1506. doi: 10.1128/jvi.61.5.1495-1506.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jenson H. B., Rabson M. S., Miller G. Palindromic structure and polypeptide expression of 36 kilobase pairs of heterogeneous Epstein-Barr virus (P3HR-1) DNA. J Virol. 1986 May;58(2):475–486. doi: 10.1128/jvi.58.2.475-486.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kearney J. F., Cooper M. D., Lawton A. R. B cell differentiation induced by lipopolysaccharide. IV. Development of immunoglobulin class restriction in precursors of IgG-synthesizing cells. J Immunol. 1976 Nov;117(5 Pt 1):1567–1572. [PubMed] [Google Scholar]
- King W., Dambaugh T., Heller M., Dowling J., Kieff E. Epstein-Barr virus DNA XII. A variable region of the Epstein-Barr virus genome is included in the P3HR-1 deletion. J Virol. 1982 Sep;43(3):979–986. doi: 10.1128/jvi.43.3.979-986.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kintner C. R., Sugden B. The structure of the termini of the DNA of Epstein-Barr virus. Cell. 1979 Jul;17(3):661–671. doi: 10.1016/0092-8674(79)90273-3. [DOI] [PubMed] [Google Scholar]
- Krowczynska A. M., Rudders R. A., Krontiris T. G. The human minisatellite consensus at breakpoints of oncogene translocations. Nucleic Acids Res. 1990 Mar 11;18(5):1121–1127. doi: 10.1093/nar/18.5.1121. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsuo T., Heller M., Petti L., O'Shiro E., Kieff E. Persistence of the entire Epstein-Barr virus genome integrated into human lymphocyte DNA. Science. 1984 Dec 14;226(4680):1322–1325. doi: 10.1126/science.6095452. [DOI] [PubMed] [Google Scholar]
- Mowatt M. R., Dunnick W. A. DNA sequence of the murine gamma 1 switch segment reveals novel structural elements. J Immunol. 1986 Apr 1;136(7):2674–2683. [PubMed] [Google Scholar]
- Nakamura Y., Leppert M., O'Connell P., Wolff R., Holm T., Culver M., Martin C., Fujimoto E., Hoff M., Kumlin E. Variable number of tandem repeat (VNTR) markers for human gene mapping. Science. 1987 Mar 27;235(4796):1616–1622. doi: 10.1126/science.3029872. [DOI] [PubMed] [Google Scholar]
- Nonoyama M., Pagano J. S. Separation of Epstein-Barr virus DNA from large chromosomal DNA in non-virus-producing cells. Nat New Biol. 1972 Aug 9;238(84):169–171. doi: 10.1038/newbio238169a0. [DOI] [PubMed] [Google Scholar]
- Patton D. F., Shirley P., Raab-Traub N., Resnick L., Sixbey J. W. Defective viral DNA in Epstein-Barr virus-associated oral hairy leukoplakia. J Virol. 1990 Jan;64(1):397–400. doi: 10.1128/jvi.64.1.397-400.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabson M., Gradoville L., Heston L., Miller G. Non-immortalizing P3J-HR-1 Epstein-Barr virus: a deletion mutant of its transforming parent, Jijoye. J Virol. 1982 Dec;44(3):834–844. doi: 10.1128/jvi.44.3.834-844.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabson M., Heston L., Miller G. Identification of a rare Epstein-Barr virus variant that enhances early antigen expression in Raji cells. Proc Natl Acad Sci U S A. 1983 May;80(9):2762–2766. doi: 10.1073/pnas.80.9.2762. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sato H., Takimoto T., Tanaka S., Tanaka J., Raab-Traub N. Concatameric replication of Epstein-Barr virus: structure of the termini in virus-producer and newly transformed cell lines. J Virol. 1990 Nov;64(11):5295–5300. doi: 10.1128/jvi.64.11.5295-5300.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sen D., Gilbert W. Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 1988 Jul 28;334(6180):364–366. doi: 10.1038/334364a0. [DOI] [PubMed] [Google Scholar]
- Shimizu A., Honjo T. Immunoglobulin class switching. Cell. 1984 Apr;36(4):801–803. doi: 10.1016/0092-8674(84)90029-1. [DOI] [PubMed] [Google Scholar]
- Sixbey J. W., Shirley P., Sloas M., Raab-Traub N., Israele V. A transformation-incompetent, nuclear antigen 2-deleted Epstein-Barr virus associated with replicative infection. J Infect Dis. 1991 May;163(5):1008–1015. doi: 10.1093/infdis/163.5.1008. [DOI] [PubMed] [Google Scholar]
- Szurek P., Petrini J., Dunnick W. Complete nucleotide sequence of the murine gamma 3 switch region and analysis of switch recombination sites in two gamma 3-expressing hybridomas. J Immunol. 1985 Jul;135(1):620–626. [PubMed] [Google Scholar]
- Tan E. M. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151. doi: 10.1016/s0065-2776(08)60641-0. [DOI] [PubMed] [Google Scholar]
- Wahls W. P., Wallace L. J., Moore P. D. Hypervariable minisatellite DNA is a hotspot for homologous recombination in human cells. Cell. 1990 Jan 12;60(1):95–103. doi: 10.1016/0092-8674(90)90719-u. [DOI] [PubMed] [Google Scholar]
- Walling D. M., Edmiston S. N., Sixbey J. W., Abdel-Hamid M., Resnick L., Raab-Traub N. Coinfection with multiple strains of the Epstein-Barr virus in human immunodeficiency virus-associated hairy leukoplakia. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6560–6564. doi: 10.1073/pnas.89.14.6560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams M., Maizels N. LR1, a lipopolysaccharide-responsive factor with binding sites in the immunoglobulin switch regions and heavy-chain enhancer. Genes Dev. 1991 Dec;5(12A):2353–2361. doi: 10.1101/gad.5.12a.2353. [DOI] [PubMed] [Google Scholar]