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T Yokota, K Konno, S Shigeta, A Verbruggen and E De Clercq
The incorporation of (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU) into DNA of varicella-zoster virus (VZV)-infected human embryo fibroblasts was studied, using thymidine kinase-positive (TK+) and thymidine kinase- negative (TK-) VZV strains. [125I]IVDU was taken up by cells infected with TK+ VZV-, but not by TK- VZV- or mock-infected cells. [125I]IVDU was incorporated into both VZV DNA and cellular DNA of TK+ VZV-infected cells. When the cells were exposed to 0.3 microM IVDU, a more marked shift was noted in the buoyant density of viral DNA than of host DNA. In contrast, the DNAs isolated from TK- VZV- or mock-infected cells did not exhibit a detectable incorporation of [125I]IVDU. [125I] IVDU- labeled VZV DNA was purified from the viral nucleocapsids of TK+ VZV- infected cells. Substitution of no more than 0.1-1% of the thymidine residues in the VZV DNA by IVDU seemed to suffice to inhibit the replication of VZV.
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L. Li, G. E. Dutschman, E. A. Gullen, E. Tsujii, S. P. Grill, Y. Choi, C. K. Chu, and Y.-c. Cheng Metabolism and Mode of Inhibition of Varicella-Zoster Virus by L-beta -5-Bromovinyl-(2-hydroxymethyl)-(1,3-dioxolanyl)uracil Is Dependent on Viral Thymidine Kinase Mol. Pharmacol., November 1, 2000; 58(5): 1109 - 1114. [Abstract] [Full Text] |
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