Persistent productive Epstein-Barr virus replication in normal epithelial cells in vivo

Productive Epstein-Barr virus (EBV) replication characterizes hairy leukopl akia, an oral epithelial lesion typically occurring in individuals infected with human immunodeficiency virus (HIV). Serial tongue biopsy specimens we re obtained from HIV-infected subjects before, during, and after valacyclov ir treatment. EBV replication was detected by Southern hybridization to lin ear terminal EBV genome fragments, reverse-transcriptase polymerase chain r eaction amplification of EBV replicative gene transcripts, immunohistochemi cal detection of EBV replicative protein, and in situ hybridization to EBV DNA. EBV replication was detected in both hairy leukoplakia and normal tong ue tissues. Valacyclovir treatment completely abrogated EBV replication in vivo, resulting in resolution of hairy leukoplakia when it was present. EBV replication returned in normal tongue epithelial cells after valacyclovir treatment. These data suggest that normal oral epithelium supports persiste nt EBV infection in individuals infected with HIV and that productive EBV r eplication is necessary but not sufficient for the pathogenesis of oral hai ry leukoplakia.