Associate Physician
Brigham and Women's Hospital

fwang@rics.bwh.harvard.edu

Our research focuses on the molecular biology, pathogenesis, and therapy of Epstein-Barr virus infection and associated malignancies. We use experimental animal model systems and translational human studies to better understand the virology and immunology of EBV infection in the context of an intact organism and to develop new approaches for immunotherapy.

We have pioneered the use of non-human primates as the most authentic animal model for EBV infection in humans. Old World primates were known to be naturally infected with B lymphotropic herpesviruses, or lymphocryptoviruses (LCV) closely related to Epstein-Barr virus. Like EBV in humans, these simian LCV infect nearly all individuals by adulthood and cause persistent asymptomatic infection for the life of the host. Simian LCV-induced B cell tumors can develop when the animals are immunosuppressed by SIV infection analogous to the EBV-induced tumors occurring in AIDS and transplant patients. LCV-naive macaques can be experimentally infected by the natural route of infection to reproduce EBV infection in humans. We have cloned and sequenced the entire rhesus LCV genome and have developed a genetic system for making mutant rhesus LCV. Ongoing projects focus on how specific viral genes contribute to persistent infection, what immune responses are critical for control of persistent infection, and how potential viral immune evasion mechanisms contribute to successful infection in the context of the natural host.

A better understanding of EBV virology and immunology is also being applied to translational studies in humans with EBV-associated nasopharyngeal carcinoma to develop more effective immunotherapy for EBV-induced malignancies. In EBV-induced cancers, virus proteins act as foreign tumor markers that can be successfully attacked by the administration of EBV-specific T cells expanded in vitro. Ongoing clinical and laboratory studies are focused on dissecting which EBV-specific T cells are most important for clinical efficacy and developing improved strategies for generating more active EBV-specific T cells for immunotherapy.

Moghaddam A, Rosenzweig M, Lee-Parritz D, Annis B, Johnson RP, Wang F. An animal model for acute and persistent Epstein-Barr virus infection. Science. 1997 Jun 27;276(5321):2030-3. [abstract]

Rivailler P, Jiang H, Cho YG, Quink C, Wang F. Complete nucleotide sequence of the rhesus lymphocryptovirus: Genetic validation for an Epstein-Barr virus animal model. J Virol. 2002 Jan;76(1):421-6. [abstract]

Rivailler P, Carville A, Kaur A, Rao P, Quink C, Kutok JL, Westmoreland S, Klumpp S, Simon M, Aster JC, Wang F. Experimental rhesus lymphocryptovirus infection in immunosuppressed macaques: an animal model for Epstein-Barr virus pathogenesis in the immunosuppressed host.Blood. 2004 Sep 1;104(5):1482-9. Epub 2004 May 18. [abstract]

Fogg MH, Kaur A, Cho YG, Wang F. The CD8+ T-cell response to an Epstein-Barr virus-related gammaherpesvirus infecting rhesus macaques provides evidence for immune evasion by the EBNA-1 homologue.J Virol. 2005 Oct;79(20):12681-91. [abstract]