tailieunhanh - Báo cáo khoa học: Initiation of JC virus DNA replication in vitro by human and mouse DNA polymerase a-primase

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 | Eur. J. Biochem. 270 2030-2037 2003 FEBS 2003 doi Initiation of JC virus DNA replication in vitro by human and mouse DNA polymerase a-primase Richard W. P. Smith1 and Heinz-Peter Nasheuer1 2 1Abteilung Biochemie Institut fur Molekulare Biotechnologie Jena Germany 2National University of Ireland Galway Department of Biochemistry Galway Ireland 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 replication of the related human pathogenic polyomavirus JC virus JCV can be supported in 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. Keywords DNA replication initiation DNA polymerase a-primase species specificity polyomavirus. Polyomavirus DNA replication has served as a model system to study eukaryotic DNA replication 1 2 . JC virus JCV belongs to the polyomavirus family and is the causative agent of progressive multifocal leukoencephalopathy in immunocompromised humans reviewed in 3-7 . JCV exhibits a highly restricted host range and this species specificity appears to be governed by host encoded DNA replication factors as hamster glial cells which support viral early gene transcription nevertheless fail to replicate JCV DNA 8 . JCV is closely related to simian virus 40 SV40 and to mouse polyomavirus PyV both of which show clear species specificities as lytic infection is limited to primate and mouse cells respectively 9 . The species specificities of both SV40 and PyV are regulated at the level of initiation of DNA replication 10 a process that has been .