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Journal of Virology, May 2004, p. 5194-5204, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5194-5204.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Acute Infection with Epstein-Barr Virus Targets and Overwhelms the Peripheral Memory B-Cell Compartment with Resting, Latently Infected Cells

Donna Hochberg,1 Tatyana Souza,1 Michelle Catalina,2 John L. Sullivan,2 Katherine Luzuriaga,2 and David A. Thorley-Lawson1*

Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111,1 Pediatrics and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 016052

Received 16 November 2003/ Accepted 19 January 2004

In this paper we demonstrate that during acute infection with Epstein-Barr virus (EBV), the peripheral blood fills up with latently infected, resting memory B cells to the point where up to 50% of all the memory cells may carry EBV. Despite this massive invasion of the memory compartment, the virus remains tightly restricted to memory cells, such that, in one donor, fewer than 1 in 104 infected cells were found in the naive compartment. We conclude that, even during acute infection, EBV persistence is tightly regulated. This result confirms the prediction that during the early phase of infection, before cellular immunity is effective, there is nothing to prevent amplification of the viral cycle of infection, differentiation, and reactivation, causing the peripheral memory compartment to fill up with latently infected cells. Subsequently, there is a rapid decline in infected cells for the first few weeks that approximates the decay in the cytotoxic-T-cell responses to viral replicative antigens. This phase is followed by a slower decline that, even by 1 year, had not reached a steady state. Therefore, EBV may approach but never reach a stable equilibrium.

* Corresponding author. Mailing address: Department of Pathology, Jaharis Building, Tufts University School of Medicine, 150 Harrison Ave., Boston, MA 02111. Phone: (617) 636-2726. Fax: (617) 636-2990. E-mail: david.thorley-lawson{at}tufts.edu.

Journal of Virology, May 2004, p. 5194-5204, Vol. 78, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.10.5194-5204.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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