EVIDENCE FOR REGULATION OF TRANSCRIPTION AND REPLICATION OF THE HUMANNEUROTROPIC VIRUS JCV GENOME BY THE HUMAN S-MU-BP-2 PROTEIN IN GLIAL-CELLS

Glial factor 1 (GF-1) is a partial cDNA isolated from a human brain cD NA library which encodes a truncated protein with binding ability to t he B-regulatory domain of the human neurotropic virus, JCV. GF-1 exhib its sequence homology to the central region of the newly identified hu man DNA-binding protein S mu bp-2. GF-1 appears to be a partial cDNA f or human S mu bp-2 based on its sequence homology to S mu bp-2 and the ir chromosomal co-localization. In this report, we have employed trans fection assay and have compared the ability of GF-1 and its full-lengt h form, S mu bp-2, on regulating the activity of JCV promoters in glia l cells. Our results demonstrate that, unlike GF-1 which stimulates JC V early promoter in glial cells, overexpression of S mu bp-2 exhibits no drastic effect on the transcription of the viral early promoter. Th e activity of the viral late promoter was noticeably increased by both GF-1 and S mu bp-2, although the level of induction by GF-1 was consi stently higher than that detected by S mu bp-2. Use of deletion constr ucts in co-transfection assay revealed that the B-domain of the JCV pr omoter is required for transcriptional activation by GF-1 and S mu bp- 2. Expression of GF-1 and S mu bp-2 in glial cells increased the induc ed level of JCV late gene transcription by the viral early protein, T- antigen. Examination of the viral DNA replication by DpnI assay indica ted that, unlike GF-1, S mu bp-2 has the ability to decrease the level df JCV DNA replication in glial cells. These observations suggest tha t the N-terminal portion of S mu bp-2 which encompasses several helica se motifs and/or its C-terminus, both of which are missing in GF-1, ma y confer differential effects on viral gene transcription and replicat ion. The biological importance of our findings in regulation of the JC V lytic cycle in glial cells is discussed.