Differential regulation of Epstein-Barr virus (EBV) latent gene expressionin Burkitt lymphoma cells infected with a recombinant EBV strain

Epstein-Barr virus (EBV)-negative Burkitt lymphomas (BLs) can be infected i n vitro with prototype EBV strains to study how the virus may affect the ph enotype of tumor cells. Studies thus far have concentrated on the use of tr ansforming B95-8 and nontransforming P3HR1 strains. Immunological and pheno typic differences between the sublines infected with these two strains were reported. The majority of these differences, if not all, can be attributed to the lack of EBNA-2 coding sequences in the P3HR1 strain. The recent dev elopment of a selectable Akata strain has opened up new possibilities for i nfecting epithelial and T cells as well. We infected five EBV-negative BL l ines with the recombinant Akata virus. Our results indicate that the infect ed cell lines BL28, Ramos, and DG75 express EBNA-1, EBNA-2, and LMP1, the v iral proteins associated with type III latency, and use both WK and QUK spl ices. In contrast, two EBV-negative variants of Akata and Mutu when reinfec ted displayed restricted type I latency and expressed only EBNA-1. All clon es of infected Mutu cells used the QUK splice exclusively. The usage of Qp was observed in a majority of Akata clones. Some Akata clones, however, wer e found to have double promoter usage (Qp and C/Wp) but at 4 months after i nfection did not express EBNA-2. The results demonstrate differential regul ation of EBV latency in BLs with the same recombinant viral strain and sugg est that the choice of latency type may be cell dependent. The restricted l atency observed for infected Akata and Mutu cells indicates that a BL may o pt for type I latency in the absence of immune pressure as well.