Latent Epstein-Barr virus infection in cottontop tamarins. A possible model for Epstein-Barr virus infection in humans

The association of Epstein-Barr virus (EBV) with a growing number of human malignancies underlines the importance of efforts aimed at preventing the infection with this potential carcinogen and of establishing animal models for human virus-associated tumors. Cottontop tamarins have been used in EBV vaccine studies because virus infection regularly induces lymphomas similar to those seen in human immunocompromised individuals. In recent years, several vaccines based on the gp340/220 envelope protein of EBV have been developed and shown to prevent the development of EBV-associated lymphomas in this model. Using in situ hybridization and immunohistology, we have characterized EBV infection in one nonimmunized and three immunized animals after challenge with a standard tumorigenic dose of EBV. In the nonimmunized animal, EBV-infected lymphoid cells were detected in numerous tissues showing no obvious lymphoma infiltration. Surprisingly, variable numbers of virus-carrying cells were also found in all three immunized animals that were protected against the development of virus-associated lymphoma. This observation demonstrates that vaccination does not induce sterilizing immunity against EBV infection in this model. Double labeling suggested a B cell phenotype of the majority of these cells. EBV infection of nonlymphoid cells was not observed. Analysis of viral gene expression in immunized animals suggested a restricted form of virus latency different from that seen in EBV-driven lymphomas in nonimmunized cottontop tamarins. These results raise the possibility that immunized cottontop tamarins protected against the development of EBV-driven lymphoma or animals exposed to a sublymphomagenic dose of virus may serve as a model for EBV infection in humans.