A MECHANISM OF INTERFERON ACTION

干扰素的作用机制

• 批准号: 3177702
• 负责人: ROBERT M FRIEDMAN
• 金额: $ 9.48万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-08-01 至 1991-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3177702
• 关键词: Golgi apparatus; Vesiculovirus; autoradiography; clone cells; complementary DNA; defective virus; electron microscopy; gel electrophoresis; glycosylation; immunofluorescence technique; interferons; ionophores; membrane activity; membrane permeability; membrane proteins; protein biosynthesis; protein metabolism; protein structure; protein transport; sialate; thrombospondins; tissue /cell culture; transfection; virus infection mechanism; virus morphology; virus protein; virus replication

Interferons (IFNs) have an unusual mechanism of action against some membrane-associated viruses. IFN-treated cells produce defective virus particles that have decreased infectivity because they are deficient in a membrane-associated glycoprotein. This is the principal antiviral activity of IFNs against retroviruses, but it is also an important mechanism for inhibiting the replication of vesicular stomatitis virus (VSV) in some cells such as IFN-treated LB cells which produce VSV particles of low infectivity that are deficient in VSV-G glycoprotein. In the IFN-treated cells G does not efficiently localize in the plasma membrane from which site it is ordinarily incorporated into budding VSV particles. Recent findings indicate that in IFN- treated cells the G protein of VSV is inefficiently transported to the plasma membrane from a cytoplasmic structure. Preliminary biochemical and morphological data suggest that this structure is the trans compartment of the Golgi complex (GC). The aims of this proposal are to analyze this localization in a clone of LB cells in which a large majority of the cells clearly manifest the cytoplasmic localization of G in IFN-treated cells. Experiments in IFN-treated cells will be carried out to study the morphological and biochemical localization of G. We also plan to analyze the transport of G protein within the GC. Other experiments will be focused on what biochemical effects of IFN might be involved in the inhibition of G transport such as changes in the pH of acid vesicles, in the fatty-acid composition of the cell, or in association of G with membranes. These studies may be useful in enlarging our understanding of how proteins are targeted by processing.

干扰素 (IFN) 具有不寻常的作用机制 一些膜相关病毒。 经 IFN 处理的细胞产生 有缺陷的病毒颗粒的传染性降低，因为 它们缺乏膜相关糖蛋白。 这是 干扰素对逆转录病毒的主要抗病毒活性，但它 也是抑制复制的重要机制 某些细胞中的水泡性口炎病毒 (VSV)，例如经 IFN 处理的细胞 产生低传染性 VSV 颗粒的 LB 细胞 VSV-G 糖蛋白缺乏。 在 IFN 处理的细胞中，G 不能有效地定位于 质膜通常从哪个位置结合 进入出芽的 VSV 颗粒。 最近的研究结果表明，在 IFN- 经处理的细胞，VSV 的 G 蛋白不能有效地转运至 质膜由细胞质结构构成。 初步的 生化和形态学数据表明该结构是 高尔基复合体 (GC) 的反式室。 该提案的目的是分析这种本地化 LB细胞克隆，其中大部分细胞明显 显示 IFN 处理的细胞中 G 的细胞质定位。 将在 IFN 处理的细胞中进行实验来研究 G 的形态和生化定位。我们还计划 分析 G 蛋白在 GC 内的转运。 其他 实验将集中于干扰素的生化作用 可能参与 G 转运的抑制，例如变化 酸性囊泡的 pH 值、脂肪酸组成 细胞，或G与膜的结合。 这些研究可能有助于加深我们对如何 蛋白质是加工的目标。