A MECHANISM OF INTERFERON ACTION

水泡性口炎病毒（VSV）产生的干扰素（IFN）处理 VSV（IFN）是细胞膜糖蛋白（G）和基质蛋白（M） 有缺陷，感染力有缺陷。 这种缺陷， 由于G蛋白缺乏而出现感染性，因为这种糖蛋白 VSV吸附到细胞所必需的。 我们的初步结果表明 VSV（IFN）中G的缺乏是由于其干扰， 组装，因为尽管VSV（IFN）中G缺乏，但没有 IFN处理的VSV感染细胞中细胞内G缺乏。 这 本研究将通过以下方式对这一现象进行研究：（A）定量 与正常VSV相比，测定VSV（IFN）中存在的G和M 以及与对照细胞相比，在VSV感染的、IFN处理的细胞中。 我们 还应研究细胞内糖基化和酰化的程度， 和病毒体G. (B)用放射自显影法研究G的转运， 免疫荧光、细胞分级和绘制G在 质膜。 (C)检查IFN处理的细胞是否产生 几种重要的膜结合DNA和RNA病毒群的病毒体 它们缺乏膜或其他重要蛋白质， 因此，传染性缺陷。 (D)研究是否增强 干扰素的抗病毒和细胞生长抑制作用的抗生素 衣霉素（Tm）与G缺陷的产生有关， 缺陷VSV（IFN）的研究：（一）化学类似物的影响， Tm对IFN作用的增强和对糖基化的影响;（ii）IFN 和Tm协同作用于Tm选择性抑制的转移酶; (iii)Tm是否影响IFN相关酶的诱导， 抑制蛋白质合成;和，（iv）在什么病毒组的组合 IFN和Tm协同作用。 我们认为这些研究将增加 了解干扰素的生物学作用，包括其抗病毒作用 活性和细胞生长抑制和免疫调节作用。

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.