Host species specificity of the polyomaviruses simian virus 40 (SV40) and mouse polyomavirus (PyV) has been shown to be determined by the host DNA polymerase a-primase complex involved in the initiation of both viral and host DNA replication. Here we demonstrate that DNA repli-cation of the related human pathogenic polyomavirus JC virus (JCV) can be supportedin vitro by DNA polymerase a-primase of either human or murine origin indicating that the mechanism of its strict species specificity differs from that of SV40 and PyV. Our results indicate that this may be due to differences in the interaction of JCV and SV40 large T antigens with the DNA replication initiation complex
