title: Epstein-Barr virus latent and replicative gene expression in oral hairy leukoplakia.
abstract: Oral hairy leukoplakia is an epithelial lesion of the tongue associated with productive infection by Epstein-Barr virus (EBV). However, no data concerning the pattern of EBV latent gene expression have been reported, and it remains unresolved whether true latent infection occurs in basal cell layers of oral hairy leukoplakia. We have studied six cases of oral hairy leukoplakia using monoclonal antibody immunohistology for EBV latent--EB nuclear antigen (EBNA) 1, EBNA 2 and latent membrane protein 1 (LMP 1); immediate-early (BZLF1); and replicative (EA, VCA, MA) proteins, and for the EBV-receptor (CD21 antigen). EBV DNA was demonstrated by nucleic acid in situ hybridization. Mid- to upper-zone keratinocytes contained EBV DNA and co-expressed EBNA 1, EBNA 2 (5 of 6 cases), LMP 1, BZLF1 protein, EA, VCA and MA. No EBV genome or gene expression could be demonstrated in basal or parabasal cells. Spinous keratinocytes were labelled by anti-CD21 antibodies HB5 and B2, but did not express the EBV-receptor as defined by reactivity with OKB7. The co-expression of latent and replicative infection-associated antigens is striking, indicating possible functional roles for latent proteins during the productive cycle. Our results suggest that oral hairy leukoplakia is caused by repeated direct infection of upper epithelial cells with virus from saliva or adjacent replicatively infected cells, rather than by a latent EBV infection of basal epithelial cells with a differentiation-dependent switch to productive infection as previously proposed.
authors.affiliation: Laboratory of Immunohistology, Aarhus University Hospital, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Sandvej
authors.forename: L
authors.initials: L
authors.lastname: Krenács
authors.forename: S J
authors.initials: SJ
authors.lastname: Hamilton-Dutoit
authors.forename: J L
authors.initials: JL
authors.lastname: Rindum
authors.forename: J J
authors.initials: JJ
authors.lastname: Pindborg
authors.forename: G
authors.initials: G
authors.lastname: Pallesen
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral / Q000032:analysis; D036022:Capsid Proteins; D004268:DNA-Binding Proteins / Q000032:analysis; D019309:Epstein-Barr Virus Nuclear Antigens; D015870:Gene Expression / Q000276:immunology*; D006679:HIV Seropositivity / Q000150:complications; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D007124:Immunoenzyme Techniques; D007972:Leukoplakia, Oral / Q000150:complications / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D015534:Trans-Activators; D014412:Tumor Virus Infections / Q000150:complications / Q000175:diagnosis / Q000382:microbiology*; D014763:Viral Matrix Proteins; D014764:Viral Proteins
chemical_list: D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; C063676:BZLF1 protein, Herpesvirus 4, Human; D036022:Capsid Proteins; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; C041788:Epstein-Barr viral capsid antigen; D015534:Trans-Activators; D014763:Viral Matrix Proteins; D014764:Viral Proteins