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Journal of Virology, February 2003, p. 1840-1847, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.1840-1847.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Compartmentalization and Transmission of Multiple Epstein-Barr Virus Strains in Asymptomatic Carriers

Diane Sitki-Green,1,2 Mary Covington,3 and Nancy Raab-Traub1,4*

Lineberger Comprehensive Cancer Center,1 School of Dentistry,2 Student Health Service,3 Department of Microbiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina4

Received 4 September 2002/ Accepted 24 October 2002

Infection with the Epstein-Barr virus (EBV) is often subclinical in the presence of a healthy immune response; thus, asymptomatic infection is largely uncharacterized. This study analyzed the nature of EBV infection in 20 asymptomatic immunocompetent hosts over time through the identification of EBV strain variants in the peripheral blood and oral cavity. A heteroduplex tracking assay specific for the EBV gene LMP1 precisely identified the presence of multiple EBV strains in each subject. The strains present in the peripheral blood and oral cavity were often completely discordant, indicating the existence of distinct infections, and the strains present and their relative abundance changed considerably between time points. The possible transmission of strains between the oral cavity and peripheral blood compartments could be tracked within subjects, suggesting that reactivation in the oral cavity and subsequent reinfection of B lymphocytes that reenter the periphery contribute to the maintenance of persistence. In addition, distinct virus strains persisted in the oral cavity over many time points, suggesting an important role for epithelial cells in the maintenance of persistence. Asymptomatic individuals without tonsillar tissue, which is believed to be an important source of virus for the oral cavity, also exhibited multiple strains and a cyclic pattern of transmission between compartments. This study revealed that the majority of patients with infectious mononucleosis were infected with multiple strains of EBV that were also compartmentalized, suggesting that primary infection involves the transmission of multiple strains. Both the primary and carrier states of infection with EBV are more complex than previously thought.

* Corresponding author. Mailing address: Lineberger Comprehensive Cancer Center, CB# 7295, University of North Carolina—Chapel Hill, Chapel Hill, NC 27599. Phone: (919) 966-1701. Fax: (919) 966-9673. E-mail: nrt{at}med.unc.edu.

Journal of Virology, February 2003, p. 1840-1847, Vol. 77, No. 3
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.3.1840-1847.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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