Abstract | AIMS: METHODS: RESULTS: Viruses (previously designated group D) that contain two mutations in the activating transcription factor/cAMP response element (ATF/CRE) in the LMP-1 promoter, which are known to decrease promoter activity greatly, were significantly less frequent in Hodgkin's disease than in both infectious mononucleosis (p = 0.0081) and asymptomatic EBV carriers (p = 0.0084). In some cases, the LMP-1 gene contained mutations in a recently identified cytotoxic T cell (CTL) epitope. Most viral isolates contained mutations shown to increase nuclear factor kappa B ( NF-kappa B) activation and had one of two newly identified C-terminal activation regions 3 (CTAR-3) deleted. The exon 1 Xho-I restriction site in the LMP-1 gene could be lost through a range of different mutations. CONCLUSIONS: These findings indicate selection pressure against EBV strains with weak LMP-1 promoter activity in Hodgkin's disease and thus provide further strong circumstantial evidence for the pathogenic role of EBV (and LMP-1) in this disease. Mutation of the CTL epitope suggests immune selection of EBV strains. Many EBV isolates contain functionally important mutations in the LMP-1 gene. Loss of the Xho-I restriction site should not be used as a marker of specific LMP-1 variants.
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Authors | K Sandvej, B S Andresen, X G Zhou, N Gregersen, S Hamilton-Dutoit |
Journal | Molecular pathology : MP
(Mol Pathol)
Vol. 53
Issue 5
Pg. 280-8
(Oct 2000)
ISSN: 1366-8714 [Print] England |
PMID | 11091852
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Activating Transcription Factor 1
- DNA-Binding Proteins
- EBV-associated membrane antigen, Epstein-Barr virus
- Epitopes, T-Lymphocyte
- Genetic Markers
- NF-kappa B
- Nuclear Proteins
- Trans-Activators
- Transcription Factors
- Viral Matrix Proteins
- CREB-Binding Protein
- CREBBP protein, human
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Topics |
- Activating Transcription Factor 1
- Base Sequence
- CREB-Binding Protein
- DNA-Binding Proteins
- Epitopes, T-Lymphocyte
(genetics)
- Genetic Markers
- Herpesvirus 4, Human
(genetics)
- Hodgkin Disease
(immunology, virology)
- Humans
- Infectious Mononucleosis
(immunology, virology)
- Molecular Sequence Data
- Mutation
- NF-kappa B
(genetics)
- Nuclear Proteins
(genetics)
- Polymerase Chain Reaction
- Promoter Regions, Genetic
(genetics)
- Sequence Analysis, DNA
- T-Lymphocytes, Cytotoxic
(ultrastructure)
- Trans-Activators
(genetics)
- Transcription Factors
(genetics)
- Viral Matrix Proteins
(genetics)
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