The basis for the restricted host range behavior of JC virus (JCV) in vitro was investigated by focusing on its DNA replicating activity and comparing it to that of simian virus 40 (SV40). Prototype, mutant, and hybrid JCV and SV40 DNAs were tested for their replicating activity in cells permissive for one or both of the viruses. Results from these experiments indicated that, relative to its SV40 counterpart, the JCV T antigen functioned less efficiently and was more specific in its interactions with polyomavirus DNA replication origins. The JCV T antigen exhibited a lower specific DNA binding activity than did the SV40 T antigen, which might contribute to this virus' reduced DNA replicating activity. However, the JCV protein did bind to both the JCV and SV40 replication origins with similar efficiency, indicating that the ability of the JCV T antigen to discriminate between the JCV and SV40 origins involved a step subsequent to specific DNA binding. The results also suggested that the failure of JCV to replicate to detectable levels in monkey kidney cells was due to the inefficient interactions of its T protein with the viral origin and the host replication machinery. The inability of the JCV T antigen to carry out one or more of these DNA replication functions efficiently contributes to the restricted lytic behavior of this virus.
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