Sequence analysis of EBV immediate-early gene BZLF1 and BRLF1 in lymphomas

The immediate-early (IE) genes, BZLF1 and BRLF1, play an important role in switching Epstein-Barr virus from the latent to the lytic state. The functions of the two IE genes and their respective proteins: ZEBRA and Rta have been well studied, but little is known about their DNA coding sequence variations and disease association. In order to investigate the sequence variation patterns and elucidate their association with lymphomas, BZLF1 and BRLF1 were analyzed in 26 and 33 lymphomas using PCR-direct sequencing method respectively. Three sequence variation types of BZLF1 gene were identified. The type BZLF1-A and BZLF1-B was detected in 34.6% (9/26) and 57.7% (15/26) of the tumor specimens, respectively. Among the three functional domains of ZEBRA, the transactivation domain had the most mutations. Three variation types were also identified in BRLF1 gene where type BR1-A and BR1-C were detected in 27.3% (9/33) and 69.7% (23/33) of specimens, respectively. Among the three functional domains of Rta, the dimerization domain was well conserved while multiple mutations were detected in both the DNA binding domain and the transactivation domain. The variation types BZLF1-B and BR1-C were more frequent in the lymphomas, compared with the throat washing samples from the healthy donors. These results suggest that the type BZLF1-B and BR1-C may be associated with the tumorigenesis of lymphoma. J. Med. Virol. 86: 1788–1795, 2014. © 2014 Wiley Periodicals, Inc.