Persistence and transition of Epstein-Barr virus genotypes in the pathogenesis of oral hairy leukoplakia.
This prospective study examined the persistence and transition of Epstein-Barr virus (EBV) in human immunodeficiency virus (HIV)-seropositive subjects with and without oral hairy leukoplakia, a replicative EBV-associated epithelial disease. The intrahost molecular epidemiology of EBV infection was characterized in subjects treated with valacyclovir to suppress EBV replication. Tongue epithelial tissues of HIV-seropositive subjects were found to support not only EBV replication but also persistent, nonproductive EBV infection. EBV appeared to enter the tongue from the blood reservoir of infection and, possibly, from exogenous sources as well. EBV transition from the blood to the tongue appeared to occur even during valacyclovir-mediated suppression of EBV replication, suggesting EBV entry into tongue epithelial tissue as a cell-associated latent infection. In conclusion, these results describe the persistence and transition of EBV as a dynamic interaction between the blood and epithelial reservoirs of EBV infection and suggest a role for entry, persistence, and reactivation of oral epithelial EBV in the pathogenesis of oral hairy leukoplakia.
Walling
Dennis M
DM
Division of Infectious Diseases, Department of Internal Medicine, and Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA. dwalling@utmb.edu
Etienne
Wiguins
W
Ray
Autumn J
AJ
Flaitz
Catherine M
CM
Nichols
C Mark
CM
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000627:therapeutic use; D004279:DNA, Viral / Q000737:chemistry / Q000302:isolation & purification; D004848:Epithelium / Q000821:virology; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D017733:Leukoplakia, Hairy / Q000188:drug therapy / Q000821:virology*; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D014059:Tongue / Q000821:virology; D000077483:Valacyclovir; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004279:DNA, Viral; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir