Convergent use of phosphatidic acid for hepatitis C virus and SARS-CoV-2 replication organelle formation.
1-Acylglycerol-3-Phosphate O-Acyltransferase
Acyltransferases
Autophagosomes
/ metabolism
Autophagy
COVID-19
/ virology
Cell Line
Cell Survival
Dengue Virus
HEK293 Cells
Hepacivirus
/ genetics
Humans
Membrane Proteins
Phosphatidic Acids
/ metabolism
SARS-CoV-2
/ genetics
Spike Glycoprotein, Coronavirus
Viral Nonstructural Proteins
Viral Proteins
Virus Replication
/ physiology
Zika Virus
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 12 2021
14 12 2021
Historique:
received:
06
05
2021
accepted:
22
11
2021
entrez:
15
12
2021
pubmed:
16
12
2021
medline:
6
1
2022
Statut:
epublish
Résumé
Double membrane vesicles (DMVs) serve as replication organelles of plus-strand RNA viruses such as hepatitis C virus (HCV) and SARS-CoV-2. Viral DMVs are morphologically analogous to DMVs formed during autophagy, but lipids driving their biogenesis are largely unknown. Here we show that production of the lipid phosphatidic acid (PA) by acylglycerolphosphate acyltransferase (AGPAT) 1 and 2 in the ER is important for DMV biogenesis in viral replication and autophagy. Using DMVs in HCV-replicating cells as model, we found that AGPATs are recruited to and critically contribute to HCV and SARS-CoV-2 replication and proper DMV formation. An intracellular PA sensor accumulated at viral DMV formation sites, consistent with elevated levels of PA in fractions of purified DMVs analyzed by lipidomics. Apart from AGPATs, PA is generated by alternative pathways and their pharmacological inhibition also impaired HCV and SARS-CoV-2 replication as well as formation of autophagosome-like DMVs. These data identify PA as host cell lipid involved in proper replication organelle formation by HCV and SARS-CoV-2, two phylogenetically disparate viruses causing very different diseases, i.e. chronic liver disease and COVID-19, respectively. Host-targeting therapy aiming at PA synthesis pathways might be suitable to attenuate replication of these viruses.
Identifiants
pubmed: 34907161
doi: 10.1038/s41467-021-27511-1
pii: 10.1038/s41467-021-27511-1
pmc: PMC8671429
doi:
Substances chimiques
Membrane Proteins
0
NS4B protein, Dengue virus
0
Phosphatidic Acids
0
Spike Glycoprotein, Coronavirus
0
Viral Nonstructural Proteins
0
Viral Proteins
0
spike protein, SARS-CoV-2
0
Acyltransferases
EC 2.3.-
1-Acylglycerol-3-Phosphate O-Acyltransferase
EC 2.3.1.51
AGPAT1 protein, human
EC 2.3.1.51
2-acylglycerophosphate acyltransferase
EC 2.3.1.52
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7276Subventions
Organisme : European Molecular Biology Organization (EMBO)
ID : ALTF 454-2020
Organisme : European Molecular Biology Organization (EMBO)
ID : ALTF 466-2016
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : Swiss National Science foundation (SNF Project Number 310030_173085
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation)
ID : Swiss National Science foundation (SNF Project Number 310030_173085
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : grant number 031A602A (ERASysApp SysVirDrug)
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : grant number 031A602A (ERASysApp SysVirDrug)
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Project Number 314905040 - TRR 209
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Project Number 272983813 - TRR 179
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Project Number 112927078 - TRR 83
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : Project Number 314905040 - TRR 209
Informations de copyright
© 2021. The Author(s).
Références
WHO Situation Reports. Coronavirus disease (COVID-19) Weekly Epidemiological Update and Weekly Operational Update.) (2021).
Spearman, C. W., Dusheiko, G. M., Hellard, M., Sonderup, M. & Hepatitis, C. Lancet 394, 1451–1466 (2019).
pubmed: 31631857
doi: 10.1016/S0140-6736(19)32320-7
Wolf, Y. I. et al. Origins and evolution of the Global RNA virome. mBio 9, e02329–18 (2018).
pubmed: 30482837
pmcid: 6282212
doi: 10.1128/mBio.02329-18
Neufeldt, C. J., Cortese, M., Acosta, E. G. & Bartenschlager, R. Rewiring cellular networks by members of the Flaviviridae family. Nat. Rev. Microbiol 16, 125–142 (2018).
pubmed: 29430005
pmcid: 7097628
doi: 10.1038/nrmicro.2017.170
V’Kovski, P., Kratzel, A., Steiner, S., Stalder, H. & Thiel, V. Coronavirus biology and replication: implications for SARS-CoV-2. Nat. Rev. Microbiol 19, 155–170 (2021).
pubmed: 33116300
doi: 10.1038/s41579-020-00468-6
Lamb, C. A., Yoshimori, T. & Tooze, S. A. The autophagosome: origins unknown, biogenesis complex. Nat. Rev. Mol. Cell Biol. 14, 759–774 (2013).
pubmed: 24201109
doi: 10.1038/nrm3696
Paul, D. & Bartenschlager, R. Flaviviridae replication organelles: oh, what a tangled web we weave. Annu. Rev. Virol. 2, 289–310 (2015).
pubmed: 26958917
doi: 10.1146/annurev-virology-100114-055007
Romero-Brey, I. et al. Three-dimensional architecture and biogenesis of membrane structures associated with hepatitis C virus replication. PLoS Pathog. 8, e1003056 (2012).
pubmed: 23236278
pmcid: 3516559
doi: 10.1371/journal.ppat.1003056
Cortese, M. et al. Integrative imaging reveals SARS-CoV-2-induced reshaping of subcellular morphologies. Cell Host Microbe 28, 853–866.e855 (2020).
pubmed: 33245857
pmcid: 7670925
doi: 10.1016/j.chom.2020.11.003
Snijder, E. J. et al. A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis. PLoS Biol. 18, e3000715 (2020).
pubmed: 32511245
pmcid: 7302735
doi: 10.1371/journal.pbio.3000715
Wolff, G., Melia, C. E., Snijder, E. J. & Barcena, M. Double-membrane vesicles as platforms for viral replication. Trends Microbiol. 28, 1022–1033 (2020).
pubmed: 32536523
pmcid: 7289118
doi: 10.1016/j.tim.2020.05.009
Oudshoorn, D. et al. Expression and cleavage of Middle East respiratory syndrome coronavirus nsp3-4 polyprotein induce the formation of double-membrane vesicles that mimic those associated with coronaviral RNA replication. mBio 8, e01658-17 (2017).
Paul, D., Hoppe, S., Saher, G., Krijnse-Locker, J. & Bartenschlager, R. Morphological and biochemical characterization of the membranous hepatitis C virus replication compartment. J. Virol. 87, 10612–10627 (2013).
pubmed: 23885072
pmcid: 3807400
doi: 10.1128/JVI.01370-13
Yamashita, A. et al. Glycerophosphate/Acylglycerophosphate acyltransferases. Biology 3, 801–830 (2014).
pubmed: 25415055
pmcid: 4280512
doi: 10.3390/biology3040801
Takeuchi, K. & Reue, K. Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis. Am. J. Physiol. Endocrinol. Metab. 296, E1195–E1209 (2009).
pubmed: 19336658
pmcid: 2692402
doi: 10.1152/ajpendo.90958.2008
Kooijman, E. E., Chupin, V., de Kruijff, B. & Burger, K. N. Modulation of membrane curvature by phosphatidic acid and lysophosphatidic acid. Traffic 4, 162–174 (2003).
pubmed: 12656989
doi: 10.1034/j.1600-0854.2003.00086.x
Zegarlinska, J., Piascik, M., Sikorski, A. F. & Czogalla, A. Phosphatidic acid - a simple phospholipid with multiple faces. Acta Biochim Pol. 65, 163–171 (2018).
pubmed: 29913482
doi: 10.18388/abp.2018_2592
Tanguy, E., Wang, Q., Moine, H. & Vitale, N. Phosphatidic acid: from pleiotropic functions to neuronal pathology. Front. Cell Neurosci. 13, 2 (2019).
pubmed: 30728767
pmcid: 6351798
doi: 10.3389/fncel.2019.00002
Mizumura, K., Choi, A. M. & Ryter, S. W. Emerging role of selective autophagy in human diseases. Front. Pharm. 5, 244 (2014).
doi: 10.3389/fphar.2014.00244
Fernandez-Galilea, M., Tapia, P., Cautivo, K., Morselli, E. & Cortes, V. A. AGPAT2 deficiency impairs adipogenic differentiation in primary cultured preadipocytes in a non-autophagy or apoptosis dependent mechanism. Biochem. Biophys. Res. Commun. 467, 39–45 (2015).
pubmed: 26417690
doi: 10.1016/j.bbrc.2015.09.128
Cautivo, K. M. et al. AGPAT2 is essential for postnatal development and maintenance of white and brown adipose tissue. Mol. Metab. 5, 491–505 (2016).
pubmed: 27408775
pmcid: 4921804
doi: 10.1016/j.molmet.2016.05.004
Lee, J. Y. et al. Spatiotemporal coupling of the hepatitis C virus replication cycle by creating a lipid droplet- proximal membranous replication compartment. Cell Rep. 27, 3602–3617.e3605 (2019).
pubmed: 31216478
doi: 10.1016/j.celrep.2019.05.063
Khan, I. et al. Modulation of hepatitis C virus genome replication by glycosphingolipids and four-phosphate adaptor protein 2. J. Virol. 88, 12276–12295 (2014).
pubmed: 25122779
pmcid: 4248901
doi: 10.1128/JVI.00970-14
Zhang, F. et al. Temporal production of the signaling lipid phosphatidic acid by phospholipase D2 determines the output of extracellular signal-regulated kinase signaling in cancer cells. Mol. Cell Biol. 34, 84–95 (2014).
pubmed: 24164897
pmcid: 3911278
doi: 10.1128/MCB.00987-13
Rizzo, M. A., Shome, K., Watkins, S. C. & Romero, G. The recruitment of Raf-1 to membranes is mediated by direct interaction with phosphatidic acid and is independent of association with Ras. J. Biol. Chem. 275, 23911–23918 (2000).
pubmed: 10801816
doi: 10.1074/jbc.M001553200
Prakash, P., Hancock, J. F. & Gorfe, A. A. Three distinct regions of cRaf kinase domain interact with membrane. Sci. Rep. 9, 2057 (2019).
pubmed: 30765804
pmcid: 6375958
doi: 10.1038/s41598-019-38770-w
Sakane, F., Hoshino, F. & Murakami, C. New era of diacylglycerol kinase, phosphatidic acid and phosphatidic acid-binding protein. Int. J. Mol. Sci. 21, 6794 (2020).
Yamano, K. et al. Endosomal Rab cycles regulate Parkin-mediated mitophagy. Elife 7, e31326 (2018).
Vargas, J. N. S. et al. Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy. Mol. Cell 74, 347–362.e346 (2019).
pubmed: 30853401
pmcid: 6642318
doi: 10.1016/j.molcel.2019.02.010
Holland, P. et al. HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. Nat. Commun. 7, 13889 (2016).
pubmed: 28004827
pmcid: 5412012
doi: 10.1038/ncomms13889
Knoops, K. et al. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. PLoS Biol. 6, e226 (2008).
pubmed: 18798692
pmcid: 2535663
doi: 10.1371/journal.pbio.0060226
Wolff, G. et al. A molecular pore spans the double membrane of the coronavirus replication organelle. Science 369, 1395–1398 (2020).
Welsch, S. et al. Composition and three-dimensional architecture of the dengue virus replication and assembly sites. Cell Host Microbe 5, 365–375 (2009).
pubmed: 19380115
pmcid: 7103389
doi: 10.1016/j.chom.2009.03.007
Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A. & Chen, J. Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 294, 1942–1945 (2001).
pubmed: 11729323
doi: 10.1126/science.1066015
Chu, J. Y. K. & Ou, J. J. Autophagy in HCV replication and protein trafficking. Int. J. Mol. Sci. 22, 1089 (2021).
Mori, H. et al. Induction of selective autophagy in cells replicating hepatitis C virus genome. J. Gen. Virol. 99, 1643–1657 (2018).
pubmed: 30311874
doi: 10.1099/jgv.0.001161
Shrivastava, S., Bhanja Chowdhury, J., Steele, R., Ray, R. & Ray, R. B. Hepatitis C virus upregulates Beclin1 for induction of autophagy and activates mTOR signaling. J. Virol. 86, 8705–8712 (2012).
pubmed: 22674982
pmcid: 3421755
doi: 10.1128/JVI.00616-12
Huang, H. et al. Hepatitis C virus inhibits AKT-tuberous sclerosis complex (TSC), the mechanistic target of rapamycin (MTOR) pathway, through endoplasmic reticulum stress to induce autophagy. Autophagy 9, 175–195 (2013).
pubmed: 23169238
pmcid: 3552882
doi: 10.4161/auto.22791
Pagliuso, A. et al. Golgi membrane fission requires the CtBP1-S/BARS-induced activation of lysophosphatidic acid acyltransferase delta. Nat. Commun. 7, 12148 (2016).
pubmed: 27401954
pmcid: 4945875
doi: 10.1038/ncomms12148
Jang, J.-H., Lee, C. S., Hwang, D. & Ryu, S. H. Understanding of the roles of phospholipase D and phosphatidic acid through their binding partners. Prog. Lipid Res. 51, 71–81 (2012).
Wang, H. & Tai, A. W. Nir2 is an effector of VAPs necessary for efficient hepatitis C virus replication and phosphatidylinositol 4-phosphate enrichment at the viral replication organelle. J. Virol. 93, e00742-19 (2019).
Judith, D. et al. ATG9A shapes the forming autophagosome through Arfaptin 2 and phosphatidylinositol 4-kinase IIIbeta. J. Cell Biol. 218, 1634–1652 (2019).
pubmed: 30917996
pmcid: 6504893
doi: 10.1083/jcb.201901115
Muller, C. et al. Inhibition of cytosolic phospholipase A2alpha impairs an early step of coronavirus replication in cell culture. J. Virol. 92, e01463-17 (2018).
Neufeldt, C. J. et al. ER-shaping atlastin proteins act as central hubs to promote flavivirus replication and virion assembly. Nat. Microbiol. 4, 2416–2429 (2019).
Stoeck, I. K. et al. Hepatitis C virus replication depends on endosomal cholesterol homeostasis. J. Virol. 92, e01196-17 (2018).
Fischl, W. & Bartenschlager, R. High-throughput screening using dengue virus reporter genomes. Methods Mol. Biol. 1030, 205–219 (2013).
pubmed: 23821271
doi: 10.1007/978-1-62703-484-5_17
Münster, M. et al. A reverse genetics system for zika virus based on a simple molecular cloning strategy. Viruses 10, 368 (2018).
pmcid: 6071187
doi: 10.3390/v10070368
Klein, S. et al. SARS-CoV-2 structure and replication characterized by in situ cryo-electron tomography. Nat. Commun. 11, 5885 (2020).
pubmed: 33208793
pmcid: 7676268
doi: 10.1038/s41467-020-19619-7
Wisniewski, J. R., Zougman, A., Nagaraj, N. & Mann, M. Universal sample preparation method for proteome analysis. Nat. Methods 6, 359–362 (2009).
pubmed: 19377485
doi: 10.1038/nmeth.1322
Olsen, J. V. et al. Parts per million mass accuracy on an Orbitrap mass spectrometer via lock mass injection into a C-trap. Mol. Cell Proteom. 4, 2010–2021 (2005).
doi: 10.1074/mcp.T500030-MCP200
Teo, G. et al. SAINTexpress: improvements and additional features in significance analysis of INTeractome software. J. Proteom. 100, 37–43 (2014).
doi: 10.1016/j.jprot.2013.10.023
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015).
pubmed: 25605792
pmcid: 4402510
doi: 10.1093/nar/gkv007
Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003).
pubmed: 14597658
pmcid: 403769
doi: 10.1101/gr.1239303
Ozbalci, C., Sachsenheimer, T. & Brugger, B. Quantitative analysis of cellular lipids by nano-electrospray ionization mass spectrometry. Methods Mol. Biol. 1033, 3–20 (2013).
pubmed: 23996167
doi: 10.1007/978-1-62703-487-6_1
Poenisch, M. et al. Identification of HNRNPK as regulator of hepatitis C virus particle production. PLoS Pathog. 11, e1004573 (2015).
pubmed: 25569684
pmcid: 4287573
doi: 10.1371/journal.ppat.1004573
Rieber, N., Knapp, B., Eils, R. & Kaderali, L. RNAither, an automated pipeline for the statistical analysis of high-throughput RNAi screens. Bioinformatics 25, 678–679 (2009).
pubmed: 19168909
doi: 10.1093/bioinformatics/btp014
Tabata, K. et al. Unique requirement for ESCRT factors in flavivirus particle formation on the endoplasmic reticulum. Cell Rep. 16, 2339–2347 (2016).
pubmed: 27545892
doi: 10.1016/j.celrep.2016.07.068
Prasad, V., Suomalainen, M., Hemmi, S. & Greber, U. F. Cell cycle-dependent kinase Cdk9 is a postexposure drug target against human adenoviruses. ACS Infect. Dis. 3, 398–405 (2017).
pubmed: 28434229
doi: 10.1021/acsinfecdis.7b00009
Neufeldt, C. J. et al. SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB. Preprint at https://search.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/en/ppbiorxiv-212639 (2020).
Schaller, T. et al. Analysis of hepatitis C virus superinfection exclusion by using novel fluorochrome gene-tagged viral genomes. J. Virol. 81, 4591–4603 (2007).
pubmed: 17301154
pmcid: 1900174
doi: 10.1128/JVI.02144-06
Kano, F. et al. Hydrogen peroxide depletes phosphatidylinositol-3-phosphate from endosomes in a p38 MAPK-dependent manner and perturbs endocytosis. Biochim. Biophys. Acta 1813, 784–801 (2011).
pubmed: 21277337
doi: 10.1016/j.bbamcr.2011.01.023
Zettl, F. et al. Rapid quantification of SARS-CoV-2-neutralizing antibodies using propagation-defective vesicular stomatitis virus pseudotypes. Vaccines 8, 386 (2020).
Perez-Riverol, Y. et al. The PRIDE database and related tools and resources in 2019: improving support for quantification data. Nucleic Acids Res. 47, D442–D450 (2019).
pubmed: 30395289
doi: 10.1093/nar/gky1106