Hepatitis C virus (HCV) infection is a confirmed risk factor for hepatocellular carcinoma (HCC). Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) possesses tumor suppression function that is frequently defective in HCC tumors. PTEN-Long, a translation isoform of PTEN, functions in a cell non-autonomous manner. In this study, we demonstrated that intracellular overexpression of PTEN-Long inhibits HCV replication. More importantly, we showed that treatment with extracellular PTEN-Long protein inhibits HCV replication in a dose-dependent manner. Furthermore, we showed that PTEN-Long interacts with HCV core protein and this interaction is required for HCV replication inhibition by PTEN-Long. In summary, we demonstrated, for the first time, that PTEN-Long protein, an isoform of the canonical PTEN and in the form of extracellular protein treatment, inhibits HCV replication. Our study offers an opportunity for developing additional anti-HCV agents.

丙型肝炎病毒（HCV）感染是确诊为肝细胞癌（HCC）的危险因素。在10号染色体（PTEN）上缺失的磷酸酶和张力蛋白同源物具有抑癌功能，在HCC肿瘤中经常存在缺陷。PTEN-Long（PTEN的翻译同工型）以细胞非自主方式发挥作用。在这项研究中，我们证明了PTEN-Long的细胞内过表达抑制了HCV复制。更重要的是，我们表明用细胞外PTEN长蛋白进行的治疗以剂量依赖的方式抑制HCV复制。此外，我们表明PTEN-Long与HCV核心蛋白相互作用，而这种相互作用是PTEN-Long抑制HCV复制所必需的。总而言之，我们首次证明了PTEN-Long蛋白，典范PTEN的同种型以及以细胞外蛋白处理的形式抑制HCV复制。我们的研究为开发其他抗HCV药物提供了机会。