Vesicular stomatitis virus (VSV) produced by interferon (IFN)-treated cells, VSV(IFN), is membrane glycoprotein (G) and matrix protein (M) deficient and is defective in infectivity. This defectiveness in infectivity appears due to the deficiency in G since this glycoprotein is necessary for VSV adsorbtion to cells. Our preliminary results suggest that the deficiency in G in VSV(IFN) is due to interference in its assembly, because in spite of the deficiency in G in VSV(IFN), there is no deficiency of intracellular G in IFN-treated, VSV-infected cells. This proposal will investigate this phenomenon by: (A) quantitative determination of the G and M present in VSV(IFN) as compared to normal VSV and in VSV-infected, IFN-treated cells as compared to control cells. We shall also study the extent of glycosylation and acylation of intracellular and virion G. (B) Study of the transport of G by autoradiography, immunofluorescence, cell fractionation and mapping the distribution of G on the plasma membrane. (C) Checking whether IFN-treated cells produce virions of several important membrane-associated DNA and RNA virus groups that are deficient in membrane or other important proteins and are, therefore, infectivity defective. (D) Study of whether the potentiation of IFN's antiviral and cell growth inhibitory actions by the antibiotic tunicamycin (Tm) is related to the production of G deficient, infectivity defective VSV(IFN) by studying: (i) the effects of chemical analogues of Tm on the potentiation of IFN action and on glycosylation; (ii) whether IFN and Tm act synergistically on the transferase selectively inhibited by Tm; (iii) whether Tm affects the induction of IFN-associated enzymes that inhibit protein synthesis; and, (iv) in what virus groups the combination of IFN and Tm act synergistically. We feel these studies will increase understanding of the biological actions of IFN including its antiviral activity and cell growth inhibitory and immunoregulatory effects.

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National Cancer Institute (NCI)
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U.S. Uniformed Services University of Health Science
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