Analysis of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1)gene and promoter in Hodgkin's disease isolates: selection against EBV variants with mutations in the LMP-1 promoter ATF-1/CREB-1 binding site
K. Sandvej et al., Analysis of the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP-1)gene and promoter in Hodgkin's disease isolates: selection against EBV variants with mutations in the LMP-1 promoter ATF-1/CREB-1 binding site, J CL PATH-M, 53(5), 2000, pp. 280-288
Citations number
46
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research Diagnosis & Treatment
Aims-To study the distribution of Epstein-Barr virus (EBV) variants contain
ing mutations in the latent membrane protein 1 (LMP-1) oncogene and promote
r in EBV associated Hodgkin's disease and infectious mononucleosis compared
with previous findings in asymptomatic EBV carriers.
Methods-Sequence analysis of the EBV LMP-1 promoter and gene in isolates fr
om Danish patients with Hodgkin's disease (n = 61) and infectious mononucle
osis (n = 10).
Results-Viruses (previously designated group D) that contain two mutations
in the activating transcription factor/cAMP response element (ATF/CRE) in t
he LMP-1 promoter, which are known to decrease promoter activity greatly, w
ere significantly less frequent in Hodgkin's disease than in both infectiou
s mononucleosis (p = 0.0081) and asymptomatic EBV carriers (p = 0.0084). In
some cases, the LMP-I gene contained mutations in a recently identified cy
totoxic 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 ran
ge of different mutations.
Conclusions-These findings indicate selection pressure against EBV strains
with weak LMP-I promoter activity in Hodgkin's disease and thus provide fur
ther strong circumstantial evidence for the pathogenic role of EBV land LMP
-I) in this disease. Mutation of the CTL epitope suggests immune selection
of EBV strains. Many EBV isolates contain functionally important mutations
in the LMF-1 gene. Loss of the Xho-I restriction site should not be used as
a marker of specific LMP-1 variants.