Screening siRNAs against host glycosylation pathways to develop novel antiviral agents against hepatitis B virus
Screening siRNAs against host glycosylation pathways to develop novel antiviral agents against hepatitis B virus
复制标题
DOI：
10.1111/hepr.13552
复制
发表时间：
2020-08-24
影响因子：
4.2
通讯作者：
Narimatsu，Hisashi
中科院分区：
文献类型：
--
作者：
Ito，Kiyoaki;Angata，Kiyohiko;Narimatsu，Hisashi
AimHepatitis B virus (HBV) relies on glycosylation for crucial functions, such as entry into host cells, proteolytic processing and protein trafficking. The aim of this study was to identify candidate molecules for the development of novel antiviral agents against HBV using an siRNA screening system targeting the host glycosylation pathway.MethodsHepG2.2.15.7 cells that consistently produce HBV were employed for our in vitro study. We investigated the effects of siRNAs that target 88 different host glycogenes on hepatitis B surface antigen (HBsAg) and HBV DNA secretion using the siRNA screening system.ResultsWe identified four glycogenes that reduced HBsAg and/or HBV DNA secretion; however, the observed results for two of them may be due to siRNA off‐target effects. Knocking downST8SIA3, a member of the sialyltransferase family, significantly reduced both HBsAg and HBV DNA secretion. Knocking downGALNT7, which transfersN‐acetylgalactosamine to initiateO‐linked glycosylation in the Golgi apparatus, also significantly reduced both HBsAg and HBV DNA levels.ConclusionsThese results showed that knocking down theST8SIA3andGALNT7glycogenes inhibited HBsAg and HBV DNA secretion in HepG2.2.15.7 cells, indicating that the host glycosylation pathway is important for the HBV life cycle and could be a potential target for the development of novel anti‐HBV agents.
