Expression of the BNLF-1 oncogene of Epstein-Barr virus in the skin of transgenic mice induces hyperplasia and aberrant expression of keratin 6.
The BNLF-1 gene of Epstein-Barr virus (EBV) encodes the latent membrane protein (LMP), one of the putative oncogene products of the virus. This gene has been expressed from two different enhancer-promoter constructs in transgenic mice, to determine its biological activity and possible contribution to oncogenesis. While transgenic mice expressing LMP in many tissues demonstrated poor viability, expression of LMP specifically in the epidermis induces a phenotype of hyperplastic dermatosis. Concomitant with the expression of LMP in this tissue (and in the esophagus) is an induction of the expression of a hyperproliferative keratin, K6, at aberrant locations within the epidermis. The epithelial hyperplastic phenotype caused by the LMP-encoding transgenes implies that the LMP plays a role in the acanthotic condition of the tongue epithelium in the human EBV- and HIV-associated syndrome oral hairy leukoplakia, as well as possibly predisposing the nasopharyngeal epithelium to carcinogenesis.
Department of Biology, Princeton University, New Jersey 08544.
J B
JB
Wilson
W
W
Weinberg
R
R
Johnson
S
S
Yuspa
A J
AJ
Levine
D000818:Animals; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015342:DNA Probes; D004195:Disease Models, Animal; D015870:Gene Expression; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia; D007633:Keratins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D009857:Oncogenes; D010641:Phenotype; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D012867:Skin / Q000473:pathology*; D014158:Transcription, Genetic; D014763:Viral Matrix Proteins / Q000235:genetics*
D015342:DNA Probes; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D014763:Viral Matrix Proteins; D007633:Keratins; D004247:DNA; D011505:Protein-Tyrosine Kinases