Construction and characterization of hybrid polyomavirus genomes

Several studies have suggested that certain unique features of the JC virus (JCV) regulatory region are responsible for the restricted lytic and transforming activities of this virus in vitro. To pursue this possibility, we have constructed hybrid polyomavirus genomes by exchanging the regulatory sequences of JCV, BK virus (BKV), and simian virus 40 (SV40). The host range of JCV was not expanded by the substitution of the BKV or SV40 regulatory signals; such hybrids were nonviable even in primary human fetal glial cells, the sole permissive cell for JCV. However, chimeric DNAs containing JCV regulatory sequences and BKV- or SV40-coding sequences were lytically active, indicating that the BKV and SV40 T proteins were capable of effectively interacting with the JCV replication and transcription signals to yield infectious hybrid viruses. Although JCV regulatory sequences and coding sequences both contributed to the restricted lytic activity of this virus, it appears that the latter sequences, most likely hose encoding the T protein, have a greater influence on this behavior.