Convergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation

• DOI: 10.1038/s41467-021-27511-1
• Publication Date: 2021-12-14T11:03:55Z
• Authors: Keisuke Tabata; Vibhu Prasad; David Paul; Ji-Young Lee; Minh-Tu Pham; Woan-Ing Twu; Christopher J. Ne...; Mirko Cortese; Berati Cerikan; Yannick Stahl; Sebastian Joecks; Cong Si Tran; Christian Lüchten...; Philip V’kovski; Katrin Hörmann; André C. Müller; Carolin Zitzmann; Uta Haselmann; Jürgen Beneke; Lars Kaderali; Holger Erfle; Volker Thiel; Volker Lohmann; Giulio Superti-Furga; Britta Brügger; Ralf Bartenschlager
• Keywords: Organelle; Replication; Sars virus

Double membrane vesicles (DMVs) serve as replication organelles of plus-strand RNA viruses such hepatitis C virus (HCV) and SARS-CoV-2. Viral DMVs are morphologically analogous to formed during autophagy, but lipids driving their biogenesis largely unknown. Here we show that production the lipid phosphatidic acid (PA) by acylglycerolphosphate acyltransferase (AGPAT) 1 2 in ER is important for DMV viral autophagy. Using HCV-replicating cells model, found AGPATs recruited critically contribute HCV SARS-CoV-2 proper formation. An intracellular PA sensor accumulated at formation sites, consistent with elevated levels fractions purified analyzed lipidomics. Apart from AGPATs, generated alternative pathways pharmacological inhibition also impaired well autophagosome-like DMVs. These data identify host cell involved organelle SARS-CoV-2, two phylogenetically disparate causing very different diseases, i.e. chronic liver disease COVID-19, respectively. Host-targeting therapy aiming synthesis might be suitable attenuate these viruses.