Epstein-Barr virus (EBV)-infected monocytes facilitate dissemination of EBV within the oral mucosal epithelium.
Epstein-Barr virus (EBV) causes hairy leukoplakia (HL), a benign lesion of oral epithelium that occurs primarily in the setting of human immunodeficiency virus (HIV)-associated immunodeficiency. However, the mechanisms of EBV infection of oral epithelium are poorly understood. Analysis of HL tissues shows a small number of EBV-positive intraepithelial macrophages and dendritic/Langerhans cells. To investigate a role for these cells in spreading EBV to epithelial cells, we used tongue and buccal explants infected ex vivo with EBV. We showed that EBV first infects submucosal CD14(+) monocytes, which then migrate into the epithelium and spread virus to oral epithelial cells, initiating productive viral infection within the terminally differentiated spinosum and granulosum layers. Incubation of EBV-infected monocytes and oral explants with antibodies to CCR2 receptor and monocyte chemotactic protein 1 prevented entry of monocytes into the epithelium and inhibited EBV infection of keratinocytes. B lymphocytes played little part in the spread of EBV to keratinocytes in our explant model. However, cocultivation of EBV-infected B lymphocytes with uninfected monocytes in vitro showed that EBV may spread from B lymphocytes to monocytes. Circulating EBV-positive monocytes were detected in most HIV-infected individuals, consistent with a model in which EBV may be spread from B lymphocytes to monocytes, which then enter the epithelium and initiate productive viral infection of keratinocytes.
Tugizov
Sharof
S
Department of Medicine, University of California San Francisco, 513 Parnassus Ave., San Francisco, CA 94143-0512, USA. sharof.tugizov@ucsf.edu
Herrera
Rossana
R
Veluppillai
Piri
P
Greenspan
John
J
Greenspan
Deborah
D
Palefsky
Joel M
JM
D000328:Adult; D002460:Cell Line; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D007801:Langerhans Cells / Q000648:ultrastructure / Q000821:virology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000648:ultrastructure / Q000821:virology*; D009061:Mouth Mucosa / Q000166:cytology* / Q000648:ultrastructure / Q000821:virology*