Inhibition of animal virus production by means of translation inhibitors unable to penetrate normal cells

The correlation between virus and host protein synthesis, membrane leakiness, and virus production has been studied in vesicular stomatitis virus-infected L cells, herpes simplex virus (type 1)- and Sendai virus-infected 37RC cells. In all three systems, membrane leakiness, as measured by an altered permeability to low-molecular-weight translation inhibitors (e.g., hygromycin B), is detectable at a time when the cells are very actively engaged in virus protein synthesis. The alteration of the membrane increases as the virus life cycle goes on so that an almost total and specific inhibition of viral translation by hygromycin B is achieved late in infection. Although the overall protein synthesis is not shut off in Sendai virus-infected cells, a gradual replacement of host protein synthesis by viral translation parallels an increasing plasma membrane permeability to hygromycin B, which is also correlated with the ever increasing fraction of infected cells. These results indicate that cells actively engaged in viral protein synthesis have lost, at least partially, the permeability barrier that plasma membrane maintains in uninfected cells. The presence of hygromycin B in the culture medium significantly reduces the production of mature virus in the three systems studied suggesting that this approach may prove useful in the search for antiviral agents.