A MECHANISM OF INTERFERON ACTION

干扰素（IFN）有一种不寻常的作用机制， 一些膜相关病毒。 IFN处理的细胞产生 有缺陷的病毒颗粒具有降低的传染性， 它们缺乏膜结合糖蛋白。 这是 IFN对逆转录病毒的主要抗病毒活性，但它 也是一个重要的机制，抑制复制 水泡性口炎病毒（VSV）在一些细胞，如IFN-处理 LB细胞产生低感染性的VSV颗粒， 缺乏VSV-G糖蛋白。 在IFN-处理的细胞中，G不能有效地定位于细胞内。 质膜，它通常从该位点结合 变成了萌芽的VSV粒子 最近的研究结果表明，在干扰素- VSV的G蛋白被低效地转运到处理的细胞中， 从细胞质结构中分离出质膜。 初步 生物化学和形态学数据表明，这种结构是 高尔基复合体的反式隔室（GC）。 本建议的目的是分析这种本地化， LB细胞的克隆，其中大部分细胞清楚地 表明G在IFN处理的细胞中的细胞质定位。 将在IFN处理的细胞中进行实验，以研究 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 实验将集中在什么样的生物化学效应干扰素 可能参与G转运的抑制，如改变 在酸性囊泡的pH值中，在 细胞，或与膜G的协会。 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.