UP-REGULATION OF EPSTEIN-BARR VIRUS-ENCODED LATENT MEMBRANE-PROTEIN BY HUMAN-HERPESVIRUS-6 SUPERINFECTION OF EBV-CARRYING BURKITT-LYMPHOMA CELLS

The effect of HHV-6 strain A infection on the expression of Epstein-Ba rr virus-(EBV-) encoded growth transformation-associated genes in two EBV-positive Burkitt lymphoma cell lines, Akata and P3HR-3, was invest igated. The results indicate that HHV-6A upregulates the expression of the latent membrane protein LMP-1 in both cell lines. Expression of E BNA-2 was also upregulated in Akata cells following HHV-6A infection. Transfection of reporter constructs carrying the LMP-1 regulatory sequ ences (LRS; -634/+40) or its 5' deleted derivatives in Akata and in a T-lymphoblastoid cell line, J-Jhan, confirmed the presence of positive and negative regulatory elements responsive to HHV-6A infection in LM P-1 regulatory sequence (LRS). The majority of LRS constructs were und er the influence of dominant negative factors. HHV-6A was able to over ride the effect of such facto rs acting on reporter plasmids containin g the -634/-54, -324/-54, -214/ -54, a nd -106/-54 parts of LRS. The p lasmid that carried only the -54/+40 LRS region was constitutively act ive in both Akata and J-Jhan cells; in Akata, its activity was influen ced by HHV-6A. The finding that HHV-6A infection may activate LMP-1 an d EBNA-2 expression, which is essential for the immortalization of B-l ymphocytes by EBV, shows a novel aspect of the interaction between the se two herpesviruses. (C) 1998 Wiley-Liss, Inc.