Modification of membrane permeability induced by animal viruses early in infection

Abstract

The infection of mouse L cells by encephalomyocarditis (EMC) virus renders the cell permeable to several translation inhibitors to which normal cells are impermeable. The modification of membrane permeability to the aminoglycoside antibiotic hygromycin B takes place early in infection during virus adsorption and also at the time when large amounts of viral coat proteins are synthesized. The specific inhibition of protein synthesis in virus-infected cells early in infection is also observed with other translation inhibitors such as anthelmycin, gougerotin, and edeine, indicating that a general permeabilization takes place during virus adsorption. The presence of 1 m M hygromycin B in the culture medium during the first hour of EMC infection strongly reduced the production of new infectious virus. In order to understand the molecular mechanisms involved in membrane permeabilization early during EMC infection, the cells were treated with compounds known to disrupt microtubules and microfilaments and to block pinocytotic processes, e.g., vinblastine, cytochalasin B, and colchicine. However, even in the presence of those compounds the early leakiness phenomenon was still observed. The presence of concanavalin A, which binds to certain cell surface recptors, or inhibitors that block energy production (e.g., FCCP and NaNs) had no significant effects on the modification of membrane permeability. Treatment of human cells with interferon does not prevent the increase in membrane permeability after EMC infection. No viral or cellular protein synthesis is necessary for the early membrane leakiness to occur, suggesting that virions themselves are responsible for this modification. The alteration of permeability to translation inhibitors is also observed after the infection of different mammalian cell lines with different viruses such as vesicular stomatitis virus and Semliki Forest virus, two lipid-enveloped RNA-containing viruses.