Endocytosis mediates the internalization and ingestion of a variety of endogenous or exogenous substances, including virus particles, under the control of intracellular signaling pathways. We have previously reported that the complex formed between the small GTPase Ras and phosphoinositide 3-kinase (PI3K) translocates from the plasma membrane to endosomes, signaling from which thereby regulates clathrin-independent endocytosis, endosome maturation, influenza virus internalization, and infection. However, the molecular mechanism by which the Ras-PI3K complex is recruited to endosomes remains unclear. Here, we have identified the amino acid sequence responsible for endosomal localization of the Ras-PI3K complex. PI3K lacking this sequence failed to translocate to endosomes, and expression of the peptide comprising this PI3K-derived sequence inhibited clathrin-independent endocytosis, influenza virus internalization, and infection. Moreover, treatment of cells with this peptide in an arginine-rich, cell-penetrating form successfully suppressed influenza virus infection in vitro and ex vivo, making this peptide a potential therapeutic agent against influenza virus infection.Key words: signal transduction, endocytosis, endosome, imaging, influenza virus.

中文翻译：

---

来自磷酸肌醇3-激酶的肽可抑制胞吞作用和流感病毒感染。

胞吞作用在细胞内信号传导途径的控制下，介导各种内源性或外源性物质（包括病毒颗粒）的内化和摄取。我们以前曾报道过，小GTP酶Ras和磷酸肌醇3激酶（PI3K）之间形成的复合物从质膜转运到内体，从而通过信号传导调控网格蛋白非依赖性内吞作用，内体成熟，流感病毒内化和感染。然而，尚不清楚Ras-PI3K复合物被募集到内体的分子机制。在这里，我们已经确定了负责Ras-PI3K复合体内体定位的氨基酸序列。缺少此序列的PI3K无法转运至内体，包含该PI3K衍生序列的肽的表达和表达抑制了网格蛋白非依赖性内吞作用，流感病毒内在化和感染。此外，用富含精氨酸，可穿透细胞形式的这种肽处理细胞成功地抑制了体外和离体的流感病毒感染，使该肽成为对抗流感病毒感染的潜在治疗剂。关键词：信号转导，内吞作用，内体，成像，流感病毒。