A MECHANISM OF INTERFERON ACTION

干扰素(IFN)有一种不同寻常的作用机制 一些膜相关病毒。干扰素处理的细胞产生 有缺陷的病毒颗粒降低了传染性，因为 它们缺乏一种与膜相关的糖蛋白。这是 IFN的主要抗病毒活性是抗逆转录病毒，但它 也是抑制病毒复制的重要机制 水泡性口炎病毒(VSV)在某些细胞中的表达，如干扰素处理 产生低传染性VSV颗粒的Lb细胞 缺乏VSV-G糖蛋白。 在干扰素处理的细胞中，G不能有效地定位在 质膜通常从哪个部位结合 变成萌芽中的VSV粒子。最近的研究表明，在干扰素中- 经处理的细胞VSV的G蛋白被低效地转运到 由细胞质结构形成的质膜。初步 生化和形态数据表明，这种结构是 高尔基复合体(GC)的跨室。 这项建议的目的是分析这种本地化 克隆的LB细胞，其中的绝大多数细胞明显 在干扰素处理的细胞中可见G的胞浆定位。 将在干扰素处理的细胞中进行实验，以研究 G.的形态和生化定位。 分析G蛋白在GC内的转运。其他 实验将集中在干扰素的哪些生化作用上 可能参与了对G转运的抑制等变化 在酸性囊泡的pH中，在脂肪酸组成中 细胞，或G与膜的结合。 这些研究可能有助于扩大我们对 蛋白质是加工的目标。

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.