Hairy leukoplakia: Arm unusual combination of transforming and permissive Epstein-Barr virus infections

Human herpesviruses are characterized by distinct states of infection. Typi cally in permissive herpesvirus infection, abundant virus production result s in cell lysis, In latent transforming Epstein-Barr virus (EBV) infection, viral proteins that induce cell growth are expressed. The immunodeficiency -associated hairy leukoplakia (HLP) lesion is the only pathologic manifesta tion of permissive EBV infection; however, within HLP, viral proteins chara cteristic of latent infection have also been detected. In this study, we fu rther analyzed expression of EBV latent genes and investigated their contri bution to the unique histologic phenotype of HLP. Coexpression of lytic and transforming viral proteins was detected simultaneously within individual HLP keratinocytes, LMP1 has now been shown to be uniformly expressed in the affected tissue, and it is associated and colocalizes with tumor necrosis factor receptor-associated factor (TRAF) signaling molecules. Effects induc ed by activated TRAF signaling that were detected in HLP included activatio n of NF-kappa B and c-Jun terminal kinase 1 (JNK1) and upregulated expressi on of epidermal growth factor receptor (EGFR), CD40, A20, and TRAPs. This s tudy identifies a novel state of EBV infection with concurrent expression o f replicative and transforming proteins. It is probable that both replicati ve and latent proteins contribute to BLP development and induce many of the histologic features of HLP, such as acanthosis and hyperproliferation. In contrast to other permissive herpesvirus infections, expression of EBV tran sforming proteins within the permissively infected HLP tissue enables epith elial cell survival and may enhance viral replication.