Hepatitis B subviral envelope particles use the COPII machinery for intracellular transport via selective exploitation of Sec24A and Sec23B. (15th February 2020)

• Record Type: Journal Article
• Authors: Zeyen, Lisa; Döring, Tatjana; Stieler, Jens T.; Prange, Reinhild
• Is Part Of: Cellular microbiology. Volume 22:Number 6(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-02-15
• Subjects: diseases -- infection -- microbe–cell interaction -- proteomics -- viruses; Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.13181
• Languages: English
• ISSNs: 1462-5814

Abstract

Abstract: 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. Abstract : Hepatitis B virus persistence is related to the immense production of subviral particles (SVPs) build up by its S (HBV.S) envelope protein. Here we demonstrate that HBV.S utilizes the host COPII complex for ER export. Among the different COPII isoform components, HBV.S selectively hijacks Sec24A and Sec23B along with Sar1/Sec13/Sec31 to travel to SVP assembly sites at the ERGIC. Functional dissection of the pathogen—host crosstalk revealed a novel ER export code, a di‐arginine motif of HBV.S, recognized by Sec24A.