Hepatitis B virus (HBV) is a leading cause of liver disease. Its success as a human pathogen is related to the immense production of subviral envelope particles (SVPs) contributing to viral persistence by interfering with immune functions. To explore cellular pathways involved in SVP formation and egress, we investigated host-pathogen interactions. Yeast-based proteomics revealed Sec24A, a component of the coat protein complex II (COPII), as an interaction partner of the HBV envelope S domain. To understand how HBV co-opts COPII as a proviral machinery, we studied roles of key Sec proteins in HBV-expressing liver cells. Silencing of Sar1, Sec23, and Sec24, which promote COPII assembly concomitant with cargo loading, strongly diminished endoplasmic reticulum (ER) envelope export and SVP secretion. By analysing Sec paralog specificities, we unexpectedly found that the HBV envelope is a selective interaction partner of Sec24A and Sec23B whose functions could not be substituted by their related isoforms. In support, we found that HBV replication upregulated Sec24A and Sec23B transcription. Furthermore, HBV encountered the Sec24A/Sec23B complex via an interaction that involved the N-terminal half of Sec24A and a di-arginine motif of its S domain, mirroring a novel ER export code. Accordingly, an interference with the COPII/HBV cross-talk might display a tool to effectively inhibit SVP release.

中文翻译：

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乙型肝炎亚病毒包膜颗粒使用COPII机制通过选择性利用Sec24A和Sec23B进行细胞内运输。

乙型肝炎病毒（HBV）是肝脏疾病的主要原因。它作为人类病原体的成功与亚病毒包膜颗粒（SVP）的大量生产有关，通过干扰免疫功能而有助于病毒的持久性。为了探索参与SVP形成和流出的细胞途径，我们研究了宿主-病原体的相互作用。基于酵母的蛋白质组学揭示了Sec24A是外壳蛋白复合物II（COPII）的组成部分，是HBV包膜S结构域的相互作用伴侣。为了了解HBV如何将COPII作为前病毒机制，我们研究了关键Sec蛋白在表达HBV的肝细胞中的作用。Sar1，Sec23和Sec24的沉默可促进COPII组装并伴随货物装载，从而极大地减少了内质网（ER）包膜输出和SVP分泌。通过分析Sec旁白的特异性，我们意外地发现HBV包膜是Sec24A和Sec23B的选择性相互作用伴侣，其功能不能被其相关的同工型所取代。在支持方面，我们发现HBV复制上调了Sec24A和Sec23B转录。此外，HBV通过涉及Sec24A的N端一半及其S结构域的双精氨酸基序的相互作用遇到了Sec24A / Sec23B复合物，反映了新的ER出口代码。因此，对COPII / HBV串扰的干扰可能显示出有效抑制SVP释放的工具。HBV通过涉及Sec24A的N端一半和其S结构域的双精氨酸基序的相互作用遇到了Sec24A / Sec23B复合物，反映了新的ER出口代码。因此，对COPII / HBV串扰的干扰可能显示出有效抑制SVP释放的工具。HBV通过涉及Sec24A的N端一半和其S结构域的双精氨酸基序的相互作用遇到了Sec24A / Sec23B复合物，反映了新的ER出口代码。因此，对COPII / HBV串扰的干扰可能显示出有效抑制SVP释放的工具。