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PMID: 7693971 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Epstein-Barr virus recombinants with specifically mutated BCRF1 genes.

Journal of virology ·Vol. 67 ·No. 12 ·1993-12-00 ·Pages 7406-13

Swaminathan S, Hesselton R, Sullivan J, Kieff E

Abstract

Epstein-Barr virus (EBV) recombinants with specifically mutated BCRF1 genes were constructed and compared with wild-type BCRF1 recombinants derived in parallel for the ability to initiate and maintain latent infection and growth transformation in primary human B lymphocytes. A stop codon insertion after codon 116 of the 170-codon BCRF1 open reading frame or deletion of the entire gene had no effect on latent infection, B-lymphocyte proliferation into long-term lymphoblastoid cell lines (LCLs), or virus replication. LCLs infected with the stop codon recombinant were indistinguishable from wild-type recombinant-infected LCLs in tumorigenicity in SCID mice. However, mutant BCRF1 recombinant-infected cells differed from wild-type recombinant-infected cells in their inability to block gamma interferon release in cultures of permissively infected LCLs incubated with autologous human peripheral blood mononuclear cells. This is the first functional assay for BCRF1 expression from the EBV genome. BCRF1 probably plays a key role in modulating the specific and nonspecific host responses to EBV infection.

MeSH Terms
Animals B-Lymphocytes/microbiology Cell Transformation, Viral Clone Cells Gene Deletion Genes, Viral Herpesvirus 4, Human/genetics Humans Interferons/biosynthesis Interleukin-10 Leukocytes, Mononuclear Mice Mice, SCID Mutation Neoplasms, Experimental/microbiology RNA, Viral/biosynthesis Recombination, Genetic Viral Proteins/genetics Virus Latency
Chemicals
BCRF1 protein, Human herpesvirus 4 RNA, Viral Viral Proteins Interleukin-10 Interferons
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Swaminathan S
Dorrance H. Hamilton Research Laboratories, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107-6799.
Hesselton R
Sullivan J
Kieff E
References (41)
41 references, click to expand
  1. Activated lymphocytes during acute Epstein-Barr virus infection.
    J Immunol. 1987 Dec 1;139(11):3802-7 PMID: 3119718
  2. A promoter for the highly spliced EBNA family of RNAs of Epstein-Barr virus.
    J Virol. 1987 Nov;61(11):3424-30 PMID: 2822952
  3. Genetic analysis of immortalizing functions of Epstein-Barr virus in human B lymphocytes.
    Nature. 1989 Aug 3;340(6232):393-7 PMID: 2547164
  4. Mutually exclusive use of viral promoters in Epstein-Barr virus latently infected lymphocytes.
    Proc Natl Acad Sci U S A. 1989 Sep;86(17):6498-502 PMID: 2549539
  5. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones.
    J Exp Med. 1989 Dec 1;170(6):2081-95 PMID: 2531194
  6. Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation.
    Proc Natl Acad Sci U S A. 1989 Dec;86(23):9558-62 PMID: 2556717
  7. 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):6826-37 PMID: 1658376
  8. Host cell and EBNA-2 regulation of Epstein-Barr virus latent-cycle promoter activity in B lymphocytes.
    J Virol. 1992 Jan;66(1):496-504 PMID: 1309259
  9. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes.
    Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1890-3 PMID: 1371884
  10. Serum levels of lymphokines and soluble cellular receptors in primary Epstein-Barr virus infection and in patients with chronic fatigue syndrome.
    J Infect Dis. 1992 Jun;165(6):994-1000 PMID: 1316417
  11. Structure of the mouse IL-10 gene and chromosomal localization of the mouse and human genes.
    J Immunol. 1992 Jun 1;148(11):3618-23 PMID: 1350294
  12. Differential effects of IL-4 and IL-10 on IL-2-induced IFN-gamma synthesis and lymphokine-activated killer activity.
    Int Immunol. 1992 May;4(5):563-9 PMID: 1627494
  13. Epstein-Barr virus-encoded small RNAs (EBERs) do not modulate interferon effects in infected lymphocytes.
    J Virol. 1992 Aug;66(8):5133-6 PMID: 1321292
  14. In vivo production of interleukin-10 by malignant cells in AIDS lymphomas.
    Eur J Immunol. 1992 Nov;22(11):2937-42 PMID: 1330578
  15. The interleukin-10 homolog encoded by Epstein-Barr virus enhances the reactivation of virus-specific cytotoxic T cell and HLA-unrestricted killer cell responses.
    Virology. 1992 Dec;191(2):773-82 PMID: 1333123
  16. Functional characterization of human IL-10.
    Int Arch Allergy Immunol. 1992;99(1):8-15 PMID: 1336421
  17. Effects of virally expressed interleukin-10 on vaccinia virus infection in mice.
    J Virol. 1993 Dec;67(12):7623-8 PMID: 8230481
  18. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI.
    Science. 1990 Jun 8;248(4960):1230-4 PMID: 2161559
  19. Expression of interleukin-10 activity by Epstein-Barr virus protein BCRF1.
    Science. 1990 Nov 9;250(4982):830-2 PMID: 2173142
  20. IL-10, a novel growth cofactor for mature and immature T cells.
    J Immunol. 1990 Dec 15;145(12):4167-73 PMID: 2124236
  21. Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells.
    J Exp Med. 1990 Dec 1;172(6):1625-31 PMID: 2124252
  22. Epstein-Barr virus (EBV)-associated lymphoproliferative disease in the SCID mouse model: implications for the pathogenesis of EBV-positive lymphomas in man.
    J Exp Med. 1991 Jan 1;173(1):147-58 PMID: 1845872
  23. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI.
    Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1172-6 PMID: 1847510
  24. 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):1546-50 PMID: 1847527
  25. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells.
    J Immunol. 1991 May 15;146(10):3444-51 PMID: 1827484
  26. Long-term T-cell-mediated immunity to Epstein-Barr virus in man. III. Activation of cytotoxic T cells in virus-infected leukocyte cultures.
    Int J Cancer. 1979 May 15;23(5):618-25 PMID: 222691
  27. The transformation of adult but not newborn human lymphocytes by Epstein Barr virus and phytohemagglutinin is inhibited by interferon: the early suppression by T cells of Epstein Barr infection is mediated by interferon.
    J Immunol. 1981 Mar;126(3):829-33 PMID: 6161964
  28. Long-term T-cell-mediated immunity to Epstein-Barr virus.
    Cancer Res. 1981 Nov;41(11 Pt 1):4216-21 PMID: 6272965
  29. Non-immortalizing P3J-HR-1 Epstein-Barr virus: a deletion mutant of its transforming parent, Jijoye.
    J Virol. 1982 Dec;44(3):834-44 PMID: 6294333
  30. Evidence for the ontogenic precedence of suppressor T cell functions in the human neonate.
    Eur J Immunol. 1983 Jan;13(1):6-13 PMID: 6299754
  31. DNA sequence and expression of the B95-8 Epstein-Barr virus genome.
    Nature. 1984 Jul 19-25;310(5974):207-11 PMID: 6087149
  32. Secretion of gamma-interferon at the cellular level. Induction by Epstein-Barr virus.
    Scand J Immunol. 1984 Nov;20(5):425-32 PMID: 6095439
  33. Regulation of Epstein-Barr virus infection by recombinant interferons. Selected sensitivity to interferon-gamma.
    Eur J Immunol. 1985 May;15(5):520-5 PMID: 2581792
  34. Transformation by Epstein-Barr virus requires DNA sequences in the region of BamHI fragments Y and H.
    J Virol. 1985 Aug;55(2):286-97 PMID: 2991556
  35. The short unique region of the B95-8 Epstein-Barr virus genome.
    Virology. 1985 Nov;147(1):81-98 PMID: 2998073
  36. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.
    J Immunol. 1986 Apr 1;136(7):2348-57 PMID: 2419430
  37. Release of lymphokines after Epstein Barr virus infection in vitro. I. Sources of and kinetics of production of interferons and interleukins in normal humans.
    J Immunol. 1986 May 15;136(10):3636-42 PMID: 3009608
  38. Epstein-Barr virus nuclear antigen 2 specifically induces expression of the B-cell activation antigen CD23.
    Proc Natl Acad Sci U S A. 1987 May;84(10):3452-6 PMID: 3033649
  39. One-signal requirement for interferon-gamma production by human large granular lymphocytes.
    J Immunol. 1987 Aug 1;139(3):724-7 PMID: 3110282
  40. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  41. Transfer of a functional human immune system to mice with severe combined immunodeficiency.
    Nature. 1988 Sep 15;335(6187):256-9 PMID: 2970594
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.67.12.7406-7413.1993
Published
1993-12-00
Pages
7406-13
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC238205
Subset
IM
Grants
NIAID NIH HHS · AI 255-42 · United States
NCI NIH HHS · CA47006 · United States
NCI NIH HHS · NCI CA60067 · United States
External Links
PubMed source DOI: 10.1128/JVI.67.12.7406-7413.1993 PMC Full Text View journal details
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