Abstract
Basic research in Epstein-Barr virus (EBV) molecular genetics has provided means to maintain episomes in human cells, to efficiently deliver episomes with up to 150 kbp of heterologous DNA to human B lymphocytes, and to immortalize human B lymphocytes with EBV recombinants that can maintain up to 120 kbp of heterologous DNA. Episome maintenance requires an EBV nuclear protein, EBNA1, whereas immortalization of cells with EBV recombinants requires EBNA1, EBNA2, EBNA3A, EBNA3C, EBNALP, and LMP1. EBV-derived vectors are useful for experimental genetic reconstitution in B lymphocytes, a cell type frequently used in establishing repositories of human genetic deficiencies. The ability of EBV-infected cells to establish a balanced state of persistence in normal humans raises the possibility that cells infected with EBV recombinants could be useful for genetic reconstitution, in vivo.
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- 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]
- Banerjee S., Livanos E., Vos J. M. Therapeutic gene delivery in human B-lymphoblastoid cells by engineered non-transforming infectious Epstein-Barr virus. Nat Med. 1995 Dec;1(12):1303–1308. doi: 10.1038/nm1295-1303. [DOI] [PubMed] [Google Scholar]
- Cohen J. I., Kieff E. An Epstein-Barr virus nuclear protein 2 domain essential for transformation is a direct transcriptional activator. J Virol. 1991 Nov;65(11):5880–5885. doi: 10.1128/jvi.65.11.5880-5885.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cohen J. I., Wang F., Mannick J., Kieff E. Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9558–9562. doi: 10.1073/pnas.86.23.9558. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Decaussin G., Leclerc V., Ooka T. The lytic cycle of Epstein-Barr virus in the nonproducer Raji line can be rescued by the expression of a 135-kilodalton protein encoded by the BALF2 open reading frame. J Virol. 1995 Nov;69(11):7309–7314. doi: 10.1128/jvi.69.11.7309-7314.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hammerschmidt W., Sugden B. Genetic analysis of immortalizing functions of Epstein-Barr virus in human B lymphocytes. Nature. 1989 Aug 3;340(6232):393–397. doi: 10.1038/340393a0. [DOI] [PubMed] [Google Scholar]
- Izumi K. M., Kaye K. M., Kieff E. D. Epstein-Barr virus recombinant molecular genetic analysis of the LMP1 amino-terminal cytoplasmic domain reveals a probable structural role, with no component essential for primary B-lymphocyte growth transformation. J Virol. 1994 Jul;68(7):4369–4376. doi: 10.1128/jvi.68.7.4369-4376.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaye K. M., Izumi K. M., Kieff E. Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9150–9154. doi: 10.1073/pnas.90.19.9150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaye K. M., Izumi K. M., Mosialos G., Kieff E. The Epstein-Barr virus LMP1 cytoplasmic carboxy terminus is essential for B-lymphocyte transformation; fibroblast cocultivation complements a critical function within the terminal 155 residues. J Virol. 1995 Feb;69(2):675–683. doi: 10.1128/jvi.69.2.675-683.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kempkes B., Pich D., Zeidler R., Sugden B., Hammerschmidt W. Immortalization of human B lymphocytes by a plasmid containing 71 kilobase pairs of Epstein-Barr virus DNA. J Virol. 1995 Jan;69(1):231–238. doi: 10.1128/jvi.69.1.231-238.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kwong A. D., Frenkel N. The herpes simplex virus amplicon. IV. Efficient expression of a chimeric chicken ovalbumin gene amplified within defective virus genomes. Virology. 1985 Apr 30;142(2):421–425. doi: 10.1016/0042-6822(85)90351-4. [DOI] [PubMed] [Google Scholar]
- Lee M. A., Kim O. J., Yates J. L. Targeted gene disruption in Epstein-Barr virus. Virology. 1992 Jul;189(1):253–265. doi: 10.1016/0042-6822(92)90701-p. [DOI] [PubMed] [Google Scholar]
- Lee M. A., Yates J. L. BHRF1 of Epstein-Barr virus, which is homologous to human proto-oncogene bcl2, is not essential for transformation of B cells or for virus replication in vitro. J Virol. 1992 Apr;66(4):1899–1906. doi: 10.1128/jvi.66.4.1899-1906.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lewin B. Genes for SMA: multum in parvo. Cell. 1995 Jan 13;80(1):1–5. doi: 10.1016/0092-8674(95)90442-5. [DOI] [PubMed] [Google Scholar]
- Lindahl T., Adams A., Bjursell G., Bornkamm G. W., Kaschka-Dierich C., Jehn U. Covalently closed circular duplex DNA of Epstein-Barr virus in a human lymphoid cell line. J Mol Biol. 1976 Apr 15;102(3):511–530. doi: 10.1016/0022-2836(76)90331-4. [DOI] [PubMed] [Google Scholar]
- Longnecker R., Miller C. L., Miao X. Q., Tomkinson B., Kieff E. The last seven transmembrane and carboxy-terminal cytoplasmic domains of Epstein-Barr virus latent membrane protein 2 (LMP2) are dispensable for lymphocyte infection and growth transformation in vitro. J Virol. 1993 Apr;67(4):2006–2013. doi: 10.1128/jvi.67.4.2006-2013.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mannick J. B., Cohen J. I., Birkenbach M., Marchini A., Kieff E. The Epstein-Barr virus nuclear protein encoded by the leader of the EBNA RNAs is important in B-lymphocyte transformation. J Virol. 1991 Dec;65(12):6826–6837. doi: 10.1128/jvi.65.12.6826-6837.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marchini A., Cohen J. I., Wang F., Kieff E. A selectable marker allows investigation of a nontransforming Epstein-Barr virus mutant. J Virol. 1992 May;66(5):3214–3219. doi: 10.1128/jvi.66.5.3214-3219.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marchini A., Kieff E., Longnecker R. Marker rescue of a transformation-negative Epstein-Barr virus recombinant from an infected Burkitt lymphoma cell line: a method useful for analysis of genes essential for transformation. J Virol. 1993 Jan;67(1):606–609. doi: 10.1128/jvi.67.1.606-609.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marchini A., Longnecker R., Kieff E. Epstein-Barr virus (EBV)-negative B-lymphoma cell lines for clonal isolation and replication of EBV recombinants. J Virol. 1992 Aug;66(8):4972–4981. doi: 10.1128/jvi.66.8.4972-4981.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marchini A., Tomkinson B., Cohen J. I., Kieff E. BHRF1, the Epstein-Barr virus gene with homology to Bc12, is dispensable for B-lymphocyte transformation and virus replication. J Virol. 1991 Nov;65(11):5991–6000. doi: 10.1128/jvi.65.11.5991-6000.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rice S. A., Knipe D. M. Genetic evidence for two distinct transactivation functions of the herpes simplex virus alpha protein ICP27. J Virol. 1990 Apr;64(4):1704–1715. doi: 10.1128/jvi.64.4.1704-1715.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robertson E. S., Grossman S., Johannsen E., Miller C., Lin J., Tomkinson B., Kieff E. Epstein-Barr virus nuclear protein 3C modulates transcription through interaction with the sequence-specific DNA-binding protein J kappa. J Virol. 1995 May;69(5):3108–3116. doi: 10.1128/jvi.69.5.3108-3116.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robertson E. S., Tomkinson B., Kieff E. An Epstein-Barr virus with a 58-kilobase-pair deletion that includes BARF0 transforms B lymphocytes in vitro. J Virol. 1994 Mar;68(3):1449–1458. doi: 10.1128/jvi.68.3.1449-1458.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robertson E., Kieff E. Reducing the complexity of the transforming Epstein-Barr virus genome to 64 kilobase pairs. J Virol. 1995 Feb;69(2):983–993. doi: 10.1128/jvi.69.2.983-993.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sugden B., Marsh K., Yates J. A vector that replicates as a plasmid and can be efficiently selected in B-lymphoblasts transformed by Epstein-Barr virus. Mol Cell Biol. 1985 Feb;5(2):410–413. doi: 10.1128/mcb.5.2.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swaminathan S., Hesselton R., Sullivan J., Kieff E. Epstein-Barr virus recombinants with specifically mutated BCRF1 genes. J Virol. 1993 Dec;67(12):7406–7413. doi: 10.1128/jvi.67.12.7406-7413.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Swaminathan S., Tomkinson B., Kieff E. Recombinant Epstein-Barr virus with small RNA (EBER) genes deleted transforms lymphocytes and replicates in vitro. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1546–1550. doi: 10.1073/pnas.88.4.1546. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tomkinson B., Kieff E. Second-site homologous recombination in Epstein-Barr virus: insertion of type 1 EBNA 3 genes in place of type 2 has no effect on in vitro infection. J Virol. 1992 Feb;66(2):780–789. doi: 10.1128/jvi.66.2.780-789.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tomkinson B., Kieff E. Use of second-site homologous recombination to demonstrate that Epstein-Barr virus nuclear protein 3B is not important for lymphocyte infection or growth transformation in vitro. J Virol. 1992 May;66(5):2893–2903. doi: 10.1128/jvi.66.5.2893-2903.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tomkinson B., Robertson E., Yalamanchili R., Longnecker R., Kieff E. Epstein-Barr virus recombinants from overlapping cosmid fragments. J Virol. 1993 Dec;67(12):7298–7306. doi: 10.1128/jvi.67.12.7298-7306.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang F., Li X., Annis B., Faustman D. L. Tap-1 and Tap-2 gene therapy selectively restores conformationally dependent HLA Class I expression in type I diabetic cells. Hum Gene Ther. 1995 Aug;6(8):1005–1017. doi: 10.1089/hum.1995.6.8-1005. [DOI] [PubMed] [Google Scholar]
- Wang F., Tsang S. F., Kurilla M. G., Cohen J. I., Kieff E. Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1. J Virol. 1990 Jul;64(7):3407–3416. doi: 10.1128/jvi.64.7.3407-3416.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yalamanchili R., Tong X., Grossman S., Johannsen E., Mosialos G., Kieff E. Genetic and biochemical evidence that EBNA 2 interaction with a 63-kDa cellular GTG-binding protein is essential for B lymphocyte growth transformation by EBV. Virology. 1994 Nov 1;204(2):634–641. doi: 10.1006/viro.1994.1578. [DOI] [PubMed] [Google Scholar]