کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2509912 | 1557836 | 2014 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Hepatitis C virus NS5A competes with PI4KB for binding to ACBD3 in a genotype-dependent manner Hepatitis C virus NS5A competes with PI4KB for binding to ACBD3 in a genotype-dependent manner](/preview/png/2509912.png)
• ACBD3 inhibited HCV replication.
• ACBD3 bind to GT1b NS5A with a higher affinity than to GT2a NS5A.
• NS5A and PI4KB competed for association of ACBD3.
Although genotype-dependency of PI4KB involved in HCV replication has been reported, the mechanism underlying that is unknown. In this study, we found that NS5A and PI4KB competed for association of acyl-coenzyme A binding domain containing protein 3 (ACBD3), which inhibited HCV replication. ACBD3 bind to GT1b NS5A with a higher affinity than to GT2a NS5A, which was consistent with higher co-localization between PI4KB and phosphatidylinositol 4-phosphate (PI4P) in GT1b HCV-infected cells than that in GT2a HCV-infected cells. These results suggested that NS5A could rob the preexisting ACBD3/PI4KB complex to form NS5A/ACBD3 complex and PI4KB could relocate to the viral RNA replication sites to facilitate HCV replication. Our findings not only revealed the anti-HCV function of ACBD3, but also shed mechanistic light on how ACBD3 was manipulated by NS5A from different GT of HCV.
Journal: Antiviral Research - Volume 107, July 2014, Pages 50–55