title: Persistent productive Epstein-Barr virus replication in normal epithelial cells in vivo.
abstract: Productive Epstein-Barr virus (EBV) replication characterizes hairy leukoplakia, an oral epithelial lesion typically occurring in individuals infected with human immunodeficiency virus (HIV). Serial tongue biopsy specimens were obtained from HIV-infected subjects before, during, and after valacyclovir treatment. EBV replication was detected by Southern hybridization to linear terminal EBV genome fragments, reverse-transcriptase polymerase chain reaction amplification of EBV replicative gene transcripts, immunohistochemical detection of EBV replicative protein, and in situ hybridization to EBV DNA. EBV replication was detected in both hairy leukoplakia and normal tongue 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 persistent EBV infection in individuals infected with HIV and that productive EBV replication is necessary but not sufficient for the pathogenesis of oral hairy leukoplakia.
authors.affiliation: Division of Infectious Diseases, Dept. of Internal Medicine, University of Texas Medical Branch at Galveston, TX 77555-0435, USA. dwalling@utmb.edu
authors.forename: D M
authors.initials: DM
authors.lastname: Walling
authors.forename: C M
authors.initials: CM
authors.lastname: Flaitz
authors.forename: C M
authors.initials: CM
authors.lastname: Nichols
authors.forename: S D
authors.initials: SD
authors.lastname: Hudnall
authors.forename: K
authors.initials: K
authors.lastname: Adler-Storthz
mesh_terms: D000212:Acyclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D001706:Biopsy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000821:virology*; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000188:drug therapy / Q000821:virology*; D015658:HIV Infections / Q000150:complications*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D017733:Leukoplakia, Hairy / Q000188:drug therapy / Q000503:physiopathology / Q000821:virology; D014059:Tongue / Q000821:virology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; C083278:BHRF1 protein, Human herpesvirus 4; C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir