Differential effects of human recombinant interferons on the expression of two early gene products of Epstein-Barr virus.

Two human Burkitt's lymphoma (BL) cell lines, Raji and Daudi, have been previously characterized as resistant and sensitive, respectively, to the anti-Epstein-Barr virus (EBV) effects of human leukocyte interferon. These cells are equally susceptible to P3HR-1 EBV superinfection as determined by EBV early antigen (EA) expression. The cell lines were pretreated with human recombinant interferons alpha 2, beta, or gamma and subsequently superinfected with P3HR-1 EBV. Their expression of two distinct EBV early gene products was evaluated by fluorescence microscopy. Monoclonal antibodies to the diffuse (EA-D) and restricted (EA-R) components of the EA complex were used to determine the number of cells expressing each of these antigens in the treated cell lines. As previously described with human leukocyte interferon, EA-D expression in Raji cells was relatively resistant to interferon-alpha 2 pretreatment. Also, EA-D expression in Daudi cells was relatively sensitive. However, interferon alpha 2 pretreatment produced an opposite pattern with respect to the expression of EA-R in these two cell lines; Raji cells were sensitive and Daudi cells relatively resistant. Interferon beta had the most uniformly effective anti-EBV activity on both cell lines; less than 15 U/ml produced 50% inhibition of both antigens in both cell lines. EA-D expression in both cell lines was sensitive to interferon-gamma pretreatment and EA-R was resistant. These data suggest that different gene products of EBV are independently regulated by interferons based on at least three factors: (1) the host cell, (2) the type of interferon and (3) the affected gene product.