Virology Faculty Member - Frederick Wang

Frederick Wang

Brigham and Women's Hospital
Channing Labs, Infectious Disease Unit
181 Longwood Avenue
Boston, MA 02115
Tel: 617 525-4258
Fax: 617 525-4257
Email: 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.



Last Update: 10/22/2013



Publications

Moghaddam A, Rosenzweig M, Lee-Parritz D, Annis A, Johnson RP, Wang F. An
animal model for acute and persistent Epstein-Barr virus infection.
Science. 1997; 276:2030-2034.

Rivailler P, Jiang H, Cho Y, Quink C, Wang F. The complete nucleotide
sequence of the rhesus lymphocryptovirus: Genetic validation for an
Epstein-Barr virus animal model. J. Virol. 2002; 76:421-426.

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; 104:1482-1489.

Fogg MH, Kaur A, Cho YG, Wang F. The CD8+ T cell response to an
Epstein-Barr related gammaherpesvirus infecting rhesus macaques provides
evidence for immune evasion by the EBNA-1 homologue. J. Virol.
2005;79:12681-12691.



© 2013 by the President and Fellows of Harvard College