Isolation and analysis of two strongly transforming isoforms of the Epstein-Barr-Virus(EBV)-encoded latent membrane protein-1 (LMP1) from a single Hodgkin's lymphoma.
Two genes encoding the latent membrane protein 1 (LMP1) of the Epstein-Barr virus (EBV) were isolated from a single case of Hodgkin's disease (HD) and were tested for their biological activities. The LMP1 gene from the Reed-Sternberg cells contained point mutations relative to the prototype LMP1 gene, leading to amino-acid exchanges. The LMP1 gene from passenger lymphocytes showed identical point mutations, but also had an in-frame insertion of 132 base pairs within the 33-bp repeat region. This insert encoding 44 amino acids contained the sequence PSQQS, corresponding to the potential TRAF-binding motif PXQXT/S. When compared to the B95.8 gene, both HD-derived LMP1 genes showed an increase in the transformation of Rat-1 rodent fibroblasts. The transforming ability of the LMP1 gene with the insertion was greater than that of the other HD-derived LMP1, and was comparable with the highly transforming LMP1-Cao gene derived from a nasopharyngeal carcinoma. The HD-derived genes stimulated expression of the cell-surface markers, CD40 and CD54, similarly to the LMP1-B95.8 gene, while the LMP1-Cao gene had a significantly reduced ability to induce these proteins. In contrast, the LMP1-Cao transactivated an NF-kappaB-response element more efficiently than did the HD-derived genes. Transfer of the 132-bp insert alone into the B95.8 gene did not increase its transforming activity to the LMP1-Cao level, indicating that additional mutations in the LMP1 gene are necessary for modulating this function.
Mehl
A M
AM
Institut für Medizinische Mikrobiologie und Hygiene, Abteilung Virologie, Homburg, Germany.
Fischer
N
N
Rowe
M
M
Hartmann
F
F
Daus
H
H
Trümper
L
L
Pfreundschuh
M
M
Müller-Lantzsch
N
N
Grässer
F A
FA
D000328:Adult; D000595:Amino Acid Sequence; D001706:Biopsy; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D005347:Fibroblasts / Q000502:physiology; D005814:Genes, Viral; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism* / Q000821:virology; D006801:Humans; D007536:Isomerism; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000502:physiology; D010641:Phenotype; D013268:Stimulation, Chemical; D014412:Tumor Virus Infections / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000302:isolation & purification* / Q000494:pharmacology
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins