Asymptomatic primary Epstein-Barr virus infection occurs in the absence ofblood T-cell repertoire perturbations despite high levels of systemic viral load

Primary infection with the human herpesvirus, Epstein-Barr virus (EBV), may result in subclinical seroconversion or may appear as infectious mononucle osis (IM), a lymphoproliferative disease of variable severity. Why primary infection manifests differently between patients is unknown, and, given the difficulties in identifying donors undergoing silent seroconversion, littl e information has been reported. However, a longstanding assumption has bee n held that IM represents an exaggerated form of the virologic and immunolo gic events of asymptomatic infection. T-cell receptor (TCR) repertoires of a unique cohort of subclinically infected patients undergoing silent infect ion were studied, and the results highlight a fundamental difference betwee n the 2 forms of infection. In contrast to the massive T-cell expansions mo bilized during the acute symptomatic phase of IM, asymptomatic donors large ly maintain homeostatic T-cell control and peripheral blood repertoire dive rsity. This disparity cannot simply be linked to severity or spread of the infection because high levels of EBV DNA were found in the blood from both types of acute infection. The results suggest that large expansions of T ce lls within the blood during IM may not always be associated with the contro l of primary EBV infection and that they may represent an overreaction that exacerbates disease. (C) 2001 by The American Society of Hematology.