Inhibition of Host Cell Macromolecular Synthesis by Vesicular Stomatitis Virus
Poirot, Mary Kathryn
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Permalink
https://hdl.handle.net/2142/71174
Description
Title
Inhibition of Host Cell Macromolecular Synthesis by Vesicular Stomatitis Virus
Author(s)
Poirot, Mary Kathryn
Issue Date
1985
Department of Study
Microbiology
Discipline
Microbiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Microbiology
Abstract
The inhibition of host cell macromolecular syntheses by vesicular stomatitis virus (VSV) was investigated. Several existing hypotheses were tested using a variety of in vivo and in vitro techniques.
In contrast to previous reports, protein synthesis inhibition could not be explained as being due to a competition between cellular and viral mRNA species for host ribosomes. The synthesis of intracellular viral RNA was varied by using defective interfering (DI) particles and VSV mutants. Under these conditions, the extent of translational inhibition was shown to be independent of the concentrations of either intracellular or polysome-bound viral mRNA species.
The inhibition of cellular RNA synthesis by VSV had previously been attributed to a small viral RNA transcript. The present study indicated that this inhibition was reversed by the addition of several drugs that preferentially inhibit translation. Although the identity of the product was not determined the translation product was required to be newly synthesized during viral infection. On the basis of this and other studies, a model for the mechanism of inhibition of cellular RNA synthesis by means of transcription regulators composed of small RNAs and nucleic acid binding proteins is discussed.
Inhibition of RNA synthesis by VSV was investigated primarily by using the SV40 minichromosome as the target for this inhibition. The structural changes and template activities of SV40 minichromosomes from VSV infected cells were analyzed. Although previous findings suggested that inhibition of SV40 or cellular DNA synthesis was an indirect result of the inhibition of protein synthesis, experiments using a mutant of VSV provided evidence for an additional direct inhibitory effect. This direct effect was characterized by an alteration in the structure of the minichromosome resulting in the inactivation of template activities.
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