Relationship between Membrane Integrity and the Inhibition of Host Translation in Virus‐Infected Mammalian Cells

Abstract

The inhibition of host protein synthesis after picornavirus infection, and its relationship to the modification of membrane permeability has been studied. In encephalomyocarditis (EMC)-virus-infected L cells, cellular protein synthesis is reduced from the third hour after infection, at which time an inhibition in "Rb' uptake by the infected cell was observed. The bulk of viral protein synthesis takes place in a cell in which a profound modification in the ionic concentration has occurred. This is in agreement with the idea that optimal viral translation requires a higher concentration of monovalent ions as compared to cellular protein synthesis.A parallel measurement of (a) protein synthesis, (b) "RbC content, (c) membrane potential and (d) modification of permeability to hygromycin B in EMC-virus-infected and poliovirus-infected HeLa cells, indicates that in EMC-virus-infected cells a correlation exists between membrane alterations and the inhibition of host protein synthesis. This correlation was not apparent in poliovirus-infected cells, suggesting that in this system other factors, different from monovalent ion alterations, are involved in the shut-off. However, in this system, the synthesis of viral proteins also takes place when the cell nT3nbrdne has been modified and permeability to ions is altered.The analysis of the shut-off of protein synthesis and permeability modification in different cell lines infected with EMC virus or poliovirus indicates that the kinetic pattern of the shut-off is variable and depends on the cell line used and the multiplicity of infection used in each experiment.The ATP content of picornavirus-infected cells was examined throughout infection. A decrease of this nucleotide in the infected cells was apparent from the third hour post-infection and this factor could perhaps contribute to the inhibition of viral protein synthesis that occurs late in infection. Another factor that could influence this inhibition is the transport of amino acids. For instance, the transport of glycine decreased from the beginning of the infection in EMC-virus-infected cells and a leakage of methionine was also observed late in infection. These modifications in membrane permeability could contribute to the development of the cytopathic effect observed in virus-infected cells

Rotavirus infection alters Na+ and K+ homeostasis in MA-104 cells

“…It has been proposed that the increase in intracellular sodium concentration is involved in the shutoff of host cell protein synthesis (Carrasco & Lacal, 1983). A temporal correlation between the two phenomena has been described in cells infected with different viruses (Garry et al, 1979;Lacal & Carrasco, 1982;Frugulhetti & Rebello, 1989). In other systems, changes in intracellular Na + and K ÷ levels are detected after viral inhibition of cellular protein synthesis.…”

“…This change might have marked effects on the metabolism of the infected cell and may impair some of its functions before lysis or detachment from its substrate occurs. Alteration of monovalent cation levels is a common result of infection by viruses with different replication strategies including cytoplasmic naked viruses (picornavirus), enveloped viruses (rhabdovirus, alphavirus) and nuclear enveloped viruses (cytomegalovirus) (Nair, 1984;Lacal & Carrasco, 1982;Francoeur & Stanners, 1978;Garry et al, 1979;Nokta et al, 1988). Mechanisms by which homeostasis of ions is affected appear to vary between different viruses.…”

“…In other systems, changes in intracellular Na + and K ÷ levels are detected after viral inhibition of cellular protein synthesis. Therefore, they do not seem to be a primary cause of the observed inhibition (Hackstadt & Mallavia, 1982;Lacal & Carrasco, 1982;Mizzen et al, 1987;Francoeur & Stanners, 1978;Nair, 1984).…”

The Regulation of Translation in Reovirus-infected Cells

“…In other instances, such as in some reovirus-infected cells, host and viral protein synthesis co-exist, with no apparent shut-down of host translation (Walden et al, 1981 ;Detjen et al, 1982). In encephalomyocarditis (EMC) virus-infected cells, inhibition of protein synthesis appears to be related to a modification of membrane permeability which leads to changes in the ionic conditions in the cells, with the result that translation of cellular mRNA is blocked, while viral protein synthesis is still favoured (Carrasco & Smith, 1976;Carrasco, 1977;Lacal & Carrasco, 1982). The suggestion that EMC virus mRNA is preferentially translated in infected cells because it is better able to compete for a limiting factor involved in protein synthesis has also been proposed (Golini et al, 1976).…”

Enhancement of phospholipase activity during poliovirus infection

“…These modifications in membrane permeability lead to an imbalance of cell membranemaintained ionic gradients (Carrasco & Smith, 1976;Egberts et al, 1977;Lacal & Carrasco, 1982;LtpezRivas et al, 1987;Nair et al, 1979). In addition, molecules that are usually excluded by cells readily pass into the cell at the time when maximal synthesis of viral proteins is taking place (Carrasco, 1987;Contreras & Carrasco, 1979).…”