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Journal of Virology, June 2007, p. 5484-5496, Vol. 81, No. 11
0022-538X/07/$08.00+0     doi:10.1128/JVI.00171-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Epstein-Barr Virus (EBV)-Infected Monocytes Facilitate Dissemination of EBV within the Oral Mucosal Epithelium

Department of Medicine,¹ Department of Orofacial Sciences, University of California San Francisco, 513 Parnassus Ave., San Francisco, California 94143-0512²

Received 9 March 2007/ Accepted 12 March 2007

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.

Published ahead of print on 21 March 2007.

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