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Journal of Virology, April 2004, p. 3455-3461, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3455-3461.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Molecular Evidence for Rhesus Lymphocryptovirus Infection of Epithelial Cells in Immunosuppressed Rhesus Macaques

Jeffery L. Kutok,1 Sherry Klumpp,2 Meredith Simon,2,{dagger} John J. MacKey,2 Vuong Nguyen,1 Jaap M. Middeldorp,3 Jon C. Aster,1 and Fred Wang4*

Departments of Pathology,1 Medicine, BrighamWomen's Hospital, Harvard Medical School, Boston, Massachusetts 02115,4 Department of Pathology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772,2 Department of Pathology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands3

Received 10 October 2003/ Accepted 2 December 2003

Epstein-Barr virus (EBV) is a human oncogenic herpesvirus associated with epithelial cell and B-cell malignancies. EBV infection of B lymphocytes is essential for acute and persistent EBV infection in humans; however, the role of epithelial cell infection in the normal EBV life cycle remains controversial. The rhesus lymphocryptovirus (LCV) is an EBV-related herpesvirus that naturally infects rhesus macaques and can be used experimentally to model persistent B-cell infection and B-cell lymphomagenesis. We now show that the rhesus LCV can infect epithelial cells in immunosuppressed rhesus macaques and can induce epithelial cell lesions resembling oral hairy leukoplakia in AIDS patients. Electron microscopy, immunohistochemistry, and DNA-RNA in situ hybridization were used to identify the presence of a lytic rhesus LCV infection in these proliferative, hyperkeratotic, or parakeratotic epithelial cell lesions. These studies demonstrate that the rhesus LCV has tropism for epithelial cells, in addition to B cells, and is a relevant animal model system for studying the role of epithelial cell infection in EBV pathogenesis.

* Corresponding author. Mailing address: Channing Laboratory, 181 Longwood Ave., Boston, MA 02115. Phone: (617) 525-4258. Fax: (617) 525-4257. E-mail: fwang{at}rics.bwh.harvard.edu.

{dagger} Present address: Charles River Laboratories, Wilmington, Mass.

Journal of Virology, April 2004, p. 3455-3461, Vol. 78, No. 7
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.7.3455-3461.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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