Picornavirus Inhibition of Host Cell Protein Synthesis
Infection of cultured cells with many lytic viruses results in a marked decrease in the rate of cellular protein synthesis. Usually, this decrease is accompanied by increasing rates of viral protein synthesis, marked cytopathic effects, and ultimately cell death. In most cases, it is not known whether the “shut-off” of host cell protein synthesis results from an active process induced by the virus evolved for that (or some other) purpose, or whether it is merely a passive result of another viral function, such as production of large quantities of viral mRNA which compete effectively with their cellular counterparts. In the case of poliovirus, however, three types of studies suggested that the former, active type of mechanism was at work. Kinetic analysis of the rate of protein synthesis in cells synchronously infected with high multiplicities of virus showed that cellular protein synthesis could be virtually completely inhibited prior to the synthesis of significant quantities of viral RNA and protein (Summers et al., 1965). In addition, infection in the presence of 1–3 mM guanidine, which prevents detectable replication of viral RNA, nevertheless results in viral inhibition of host cell protein synthesis (Holland, 1964; Bablanian et al., 1965, Penman and Summers, 1965). Last, infection with a temperature-sensitive mutant of poliovirus that synthesizes no single-stranded RNA at restrictive temperature nevertheless induces normal inhibition of cellular protein synthesis (Hewlett et al., 1982). All of these results argue against a competition between cellular and viral mRNAs for cellular components as an explanation for the selective inhibition of cellular protein synthesis. A large body of experimental work on this subject has been performed with poliovirusinfected cells, and consequently, the major focus of this review is on the inhibiton of protein synthesis by poliovirus.
KeywordsInitiation Factor Semliki Forest Virus Ehrlich Ascites Tumor Cell Frog Virus Viral Protein Synthesis
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