Reovirus Effects on Host Cell DNA Synthesis

Studies using synchronized L cells have shown that DNA synthesis in the late part of the S phase is inhibited strongly following infection with reovirus, whereas, DNA synthesis in the early part of the S phase is relatively unaffected (Ensminger and Tamm, 1970). Infected cells enter the S phase early during infection, but later the cells are blocked in G1 (Ensminger and Tamm, 1970 Cox and Shaw, 1974). Electron-microscopic examination of the ultrastructural changes in the nuclei has indicated that the initial decrease in DNA synthesis is accompanied by decompaction of condensed chromatin 

Type 3 reovirus does not inhibit cellular DNA synthesis in all cell types. Shaw and his co-workers found that there is a differential sensitivity of normal and transformed human cells to the effect inhibition occurs in SV40 transformed WI-38 cells but not in normal WI-38 cells (Duncan et al., 1978). This differential inhibition correlates with a difference in cytopathology. Infection of transformed cells results in cell lysis by 96 hr postinfection, whereas, nontransformed cells are productively infected and continue to produce virus for days after infection without detectable cytopathology. 

Using a genetic approach, Sharpe and Fields (1981) also investigated reovirus inhibition of cellular DNA synthesis. They found that while type 3 reovirus inhibits cellular DNA synthesis in mouse L cells, type 1 reovirus exerts little or no effect on L cell DNA synthesis (Fig. 2). The different effects of type 1 and 3 reovirus on L cell DNA synthesis could not be explained by differences in the growth characteristics of these viruses in mouse L cells because both serotypes grow to the same extent and at the same rate in these cells. Furthermore, no cytopathic effects were observed in L cells at the time of inhibition of DNA synthesis. 

A series of reassortant viruses containing genome segments of type 1 Lang and type 3 Dearing were examined for their ability to inhibit L cell DNA synthesis. The reassortant viruses behaved like the type 1 or type 3 parental viruses. No intermediate pattern of DNA 

Identical results were obtained with live and UV-irradiated parental and reassortant viruses. Since inactivated as well as live reo-viruses inhibit DNA synthesis, the SI gene product and not dsRNA appears to be the viral component responsible for this inhibition. 

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