Viruses utilize cellular proteins to mediate their life cycle. However, the hepatitis B virus (HBV) life cycle is still mysterious and remains to be elucidated. Here, GRP78/BiP/HSPA5, a 78 kDa glucose‐regulated protein, was identified as a preS2 interacting protein. Pulldown assay showed the interaction of glucose‐regulated protein 78 (GRP78) with both the preS2 domain‐containing large S and middle S proteins expressed in a human hepatocellular cell line. The immunofluorescence studies revealed that the preS2 colocalized with GRP78. Interestingly, it was found that preS2 specifically bound to the ATPase domain of GRP78. To understand how GRP78 plays a role in HBV infection, stably GRP78‐expressing cells were established, which promoted HBV infectivity and replication. In contrast, knockdown of GRP78 changed the HBV antigen secretion but not the viral DNA amplification. Taken together, these results suggest that GRP78 should interact with preS2 via the ATPase domain and modulate both the HBV infectivity and HBV antigen secretion.

中文翻译：

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GRP78 在乙型肝炎病毒感染和抗原分泌中的功能作用

病毒利用细胞蛋白质来调节它们的生命周期。然而，乙型肝炎病毒（HBV）的生命周期仍然是个谜，有待阐明。在这里，GRP78/BiP/HSPA5 是一种 78 kDa 葡萄糖调节蛋白，被鉴定为 preS2 相互作用蛋白。下拉测定显示葡萄糖调节蛋白 78 (GRP78) 与在人肝细胞系中表达的包含前 S2 结构域的大 S 和中间 S 蛋白的相互作用。免疫荧光研究表明，preS2 与 GRP78 共定位。有趣的是，发现 preS2 与 GRP78 的 ATPase 结构域特异性结合。为了了解 GRP78 如何在 HBV 感染中发挥作用，建立了稳定表达 GRP78 的细胞，这促进了 HBV 的感染性和复制。相比之下，GRP78 的敲低改变了 HBV 抗原的分泌，但没有改变病毒 DNA 的扩增。总之，这些结果表明 GRP78 应该通过 ATPase 结构域与 preS2 相互作用并调节 HBV 感染性和 HBV 抗原分泌。