Specific Inhibition of Replication of Animal Viruses

Abstract

The process of virus reproduction is so closely bound up with the metabolism of the virus-infected cell that its study has been hindered by inability to distinguish experimentally between the two. The main difficulty has been the lack of specific chemical markers which would make possible the study of the synthesis of virus nucleic acids and proteins without measuring or affecting host-cell synthesis. In the exceptional instance of T2, T4, and T6 bacteriophages, which contain an unusual nucleotide, a very beautiful and comprehensive picture has been obtained of the biochemical and enzymatic changes in the virus-infected cells (1).In the last few years, however, chemical compounds have been found which can distinguish between virusinduced and cellular processes and thus the knowledge of virus-specific events in the reproduction of animal viruses has begun to advance more rapidly. The mechanisms of action of these virus-specific inhibitors bear directly on questions concerning virusspecific features of the structure, synthesis, and functions of virus nucleic acids and proteins.Virus reproduction can occur only inside a living cell, since the virus is dependent on the cell both for energy and for the building blocks that make up its substance. Various subcellular structures serve specialized functions in the mechanism of virus reproduction. The virus particle consists of a protein shell (the capsid) and a core of nucleic acid (2). The nucleic acid may be either DNA or RNA; no virus has SCIENCE, VOL. 142

Poliovirus-induced inhibition of polypeptide initiation in vitro on native polyribosomes.

“…After shaking for 20 min at 40 the suspension of ribosomes (0.2-0.4 ml) was centrifuged as above. The soluble fraction, used as a ribosomal wash fraction, was dialyzed for 4 hr against 500 volumes of ribosomal wash buffer [5 mM Tris-HCl (pH 7.4), 100 mM KCl, 0.05 mM EDTA, 5 mM 2-mercaptoethanol]. The salt-washed polyribosomal pellet was rinsed and resuspended in the standard sucrose solution.…”

“…One of the most extensively studied examples occurs during poliovirus infection, where host cell protein synthesis is inhibited relatively early in infection, prior to the appearance of appreciable amounts of viral RNA (1). Complete inhibition of host protein synthesis occurs even in the presence of guanidine (1-3), which inhibits viral RNA replication (4,5 (S-200) fractions by centrifugation in a Spinco angle 50 rotor for 50 min at 50,000 rpm. Two-milliliter microtubes, half-filled, were used.…”

Failure of Guanidine and 2-( -Hydroxybenzyl)benzimidazole to Inhibit Replication of Hepatitis A Virus In vitro

“…Moreover, experimental analysis of virus replication would be greatly facilitated if synthesis of virus RNA could be inhibited by one or both of the two chemicals (Tamm & Eggers, 1963;Sergiescu et al, 1972). To investigate these possibilities, monolayer cultures of the cell line PLC/PRF/5, which has been derived from a human hepatocellular carcinoma (Alexander et al, 1978), were inoculated with HAV strain MBB 11/5 at a multiplicity of infection (m.o.i.)…”

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

“…It is interesting to keep in mind several characteristics of the shut-off phenomenon: (a) most of viral proteins are synthesized under conditions adverse to the translation of cellular mRNAs; (b) the inhibition of host protein synthesis occurs even when the replication and expression of the viral genome is restricted, e.g. by guanidine in poliovirus-infected cells [4] or by interferon pretreatment [5]; (c) however, some viral replication is necessary for the shut-off to occur.…”