FUNCTIONAL AND PHYSICAL INTERACTION BETWEEN P53 AND BZLF1 - IMPLICATIONS FOR EPSTEIN-BARR-VIRUS LATENCY

The p53 tumor suppressor protein, which is commonly mutated in human c ancers, has been shown to interact directly with virally encoded prote ins from papillomavirus, adenovirus, and simian virus 40. The disrupti on of p53 function may be required for efficient replication of certai n viruses and may also play a role in the development of virally induc ed malignancies. Infection with Epstein-Barr virus (EBV) has been asso ciated with the development of B-cell lymphomas and nasopharyngeal car cinoma. Here we show that the EBV immediate-early protein, BZLF1 (Z), which is responsible for initiating the switch from latent to lytic in fection, can interact directly in vitro and in vivo with the tumor sup pressor protein, p53. This interaction requires the coiled-coil dimeri zation domain of the Z protein and the carboxy-terminal portion of p53 . Overexpression of wild-type p53 inhibits the ability of Z to disrupt viral latency. Likewise, Z inhibits p53-dependent transactivation in lymphoid cells. The direct interaction between Z and p53 may play a ro le in regulating the switch from latent to lytic viral infection.