Non-correlation of in vivo and in vitro parameters of Epstein-Barr virus persistence suggests heterogeneity of B cell infection

Following primary infection Epstein-Barr virus (EBV) establishes a persistent infection which is maintained for the life-time of the host. EBV can be found in a small number of circulating B cells, but the nature of the virus-cell interaction has not been fully established. Several assay systems are used to quantify persistent EBV infection, including PCR amplification of EBV DNA and spontaneous outgrowth of lymphoblastoid cell lines in culture. More recently, outgrowth of EBV-positive B cell tumours in severe combined immunodeficient (SCID) mice inoculated with peripheral blood mononuclear cells (PBMC) from normal EBV-seropositive donors has also been used to study B cell infection in vivo. In the present study we have compared the results of these two biological assay systems with PCR detection of EBV DNA and a regression assay as a measure of host T cell immunity to EBV. PBMC from ten normal EBV-seropositive donors were studied and although each test gave consistent results on repeat assays, no correlation was found between any of the assays tested. This result suggests that each assay measures a separate aspect of EBV persistence in B cells, and indicates a previously unrecognized degree of heterogeneity in the B cell population in which EBV resides.