HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hand, R. Articles by Oblin, C. Search for Related Content PubMed PubMed Citation Articles by Hand, R. Articles by Oblin, C. Agricola Articles by Hand, R. Articles by Oblin, C.

DNA Synthesis in Mengovirus-infected Cells: Mechanism of Inhibition

Departments of Medicine and Microbiology, McGill University, Montreal, Quebec, Canada

We have studied several aspects of the inhibition of DNA synthesis in Mengovirus-infected cells. In mouse L-929 cells at 5 h after infection at a multiplicity of 200 p.f.u./cell, there was a decrease in DNA synthesis. However, the rate of DNA replication fork movement, measured by equilibrium sedimentation of DNA sequentially labelled with BrdUrd and ³H-thymidine, was not significantly reduced in infected cells despite an 84% inhibition of DNA synthesis. Enzymic assay of the total cellular dTTP pool size showed it to be increased 37% in infected cells compared to controls. This was not accounted for by enhanced entry of thymidine nucleotides into the pool from either exogenous or endogenous sources, since the buoyant density of DNA pulse-labelled with ³H-BrdUrd was the same in infected and uninfected cells and there was no evidence for breakdown of DNA in infected cells. There was also a moderate decrease in the uptake of exogenous thymidine into the cell, shown by a reduction in the V_max for transport with little change in the K_m. By 6 h after infection, the dTTP pool size was slightly smaller in infected cells than in the controls and there was a marked inhibition in the rate of replication fork movement. These results show that Mengovirus infection blocks the entry of dTTP into DNA. At 5 h after infection, this block is manifested by an inhibition of initiation of new DNA chain synthesis. By 6 h, replication fork movement is also retarded and there is a more generalized derangement in DNA synthesis.

Received 26 April 1977; accepted 13 June 1977.