Integrative Functional Genomics of Hepatitis C Virus Infection Identifies Host Dependencies in Complete Viral Replication Cycle

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Hepatitis C virus (HCV) is a positive strand RNA virus that belongs to the Flaviridae family. Chronic HCV infection is a leading cause of end-stage liver disease, which is associated with significant morbidity and mortality in the world. Our recent genome-wide siRNA screen has revealed that HCV depends extensively on host factors for efficient infection and propagation. Here we systematically and functionally catalogued these host dependencies to various stages of the HCV replication cycle. Applying systems virology and functional genomics approaches with various in vitro HCV model systems, we further defined multiple previously unrecognized host factors or pathways that are involved in either HCV entry, IRES-mediated translation, RNA replication, or assembly/secretion. By bioinformatics meta-analyses and literature mining of existing publications and databases, we constructed an extensive roadmap of the cellular networks and pathways requisite for the complete HCV replication cycle. Our study yields novel insights into viral infection, pathogenesis and potential therapeutic targets. Furthermore, this study serves as a valuable reference source for subsequent work on host pathways and virus-host interactions in general.

Vyšlo v časopise: Integrative Functional Genomics of Hepatitis C Virus Infection Identifies Host Dependencies in Complete Viral Replication Cycle. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004163
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004163

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1. LiangTJ, RehermannB, SeeffLB, HoofnagleJH (2000) Pathogenesis, natural history, treatment, and prevention of hepatitis C. Annals of internal medicine 132: 296–305.

2. LiangTJ, GhanyMG (2013) Current and future therapies for hepatitis C virus infection. The New England journal of medicine 368: 1907–1917.

3. de ChasseyB, NavratilV, TafforeauL, HietMS, Aublin-GexA, et al. (2008) Hepatitis C virus infection protein network. Molecular systems biology 4: 230.

4. LiQ, BrassAL, NgA, HuZ, XavierRJ, et al. (2009) A genome-wide genetic screen for host factors required for hepatitis C virus propagation. Proceedings of the National Academy of Sciences of the United States of America 106: 16410–16415.

5. RandallG, PanisM, CooperJD, TellinghuisenTL, SukhodoletsKE, et al. (2007) Cellular cofactors affecting hepatitis C virus infection and replication. Proceedings of the National Academy of Sciences of the United States of America 104: 12884–12889.

6. TaiAW, BenitaY, PengLF, KimSS, SakamotoN, et al. (2009) A functional genomic screen identifies cellular cofactors of hepatitis C virus replication. Cell host & microbe 5: 298–307.

7. MoradpourD, PeninF, RiceCM (2007) Replication of hepatitis C virus. Nature reviews Microbiology 5: 453–463.

8. PlossA, EvansMJ (2012) Hepatitis C virus host cell entry. Current opinion in virology 2: 14–19.

9. BartenschlagerR, PeninF, LohmannV, AndreP (2011) Assembly of infectious hepatitis C virus particles. Trends in microbiology 19: 95–103.

10. FriedelCC, HaasJ (2011) Virus-host interactomes and global models of virus-infected cells. Trends in microbiology 19: 501–508.

11. KatzeMG, FornekJL, PalermoRE, WaltersKA, KorthMJ (2008) Innate immune modulation by RNA viruses: emerging insights from functional genomics. Nature reviews Immunology 8: 644–654.

12. PandaD, CherryS (2012) Cell-based genomic screening: elucidating virus-host interactions. Current opinion in virology 2: 784–792.

13. BergerKL, CooperJD, HeatonNS, YoonR, OaklandTE, et al. (2009) Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replication. Proceedings of the National Academy of Sciences of the United States of America 106: 7577–7582.

14. LupbergerJ, ZeiselMB, XiaoF, ThumannC, FofanaI, et al. (2011) EGFR and EphA2 are host factors for hepatitis C virus entry and possible targets for antiviral therapy. Nature medicine 17: 589–595.

15. ReissS, RebhanI, BackesP, Romero-BreyI, ErfleH, et al. (2011) Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment. Cell host & microbe 9: 32–45.

16. BartoschB, DubuissonJ, CossetFL (2003) Infectious hepatitis C virus pseudo-particles containing functional E1–E2 envelope protein complexes. The Journal of experimental medicine 197: 633–642.

17. LohmannV, KornerF, KochJ, HerianU, TheilmannL, et al. (1999) Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285: 110–113.

18. SongY, FriebeP, TzimaE, JunemannC, BartenschlagerR, et al. (2006) The hepatitis C virus RNA 3′-untranslated region strongly enhances translation directed by the internal ribosome entry site. Journal of virology 80: 11579–11588.

19. LindenbachBD, EvansMJ, SyderAJ, WolkB, TellinghuisenTL, et al. (2005) Complete replication of hepatitis C virus in cell culture. Science 309: 623–626.

20. WakitaT, PietschmannT, KatoT, DateT, MiyamotoM, et al. (2005) Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nature medicine 11: 791–796.

21. ZhongJ, GastaminzaP, ChengG, KapadiaS, KatoT, et al. (2005) Robust hepatitis C virus infection in vitro. Proceedings of the National Academy of Sciences of the United States of America 102: 9294–9299.

22. SteinmannE, BrohmC, KallisS, BartenschlagerR, PietschmannT (2008) Efficient trans-encapsidation of hepatitis C virus RNAs into infectious virus-like particles. Journal of virology 82: 7034–7046.

23. MasakiT, SuzukiR, SaeedM, MoriK, MatsudaM, et al. (2010) Production of infectious hepatitis C virus by using RNA polymerase I-mediated transcription. Journal of virology 84: 5824–5835.

24. MohrS, BakalC, PerrimonN (2010) Genomic screening with RNAi: results and challenges. Annual review of biochemistry 79: 37–64.

25. SigoillotFD, KingRW (2011) Vigilance and validation: Keys to success in RNAi screening. ACS chemical biology 6: 47–60.

26. AndersenSS (2000) Spindle assembly and the art of regulating microtubule dynamics by MAPs and Stathmin/Op18. Trends in cell biology 10: 261–267.

27. RoohvandF, MaillardP, LavergneJP, BoulantS, WalicM, et al. (2009) Initiation of hepatitis C virus infection requires the dynamic microtubule network: role of the viral nucleocapsid protein. The Journal of biological chemistry 284: 13778–13791.

28. WolkB, BucheleB, MoradpourD, RiceCM (2008) A dynamic view of hepatitis C virus replication complexes. Journal of virology 82: 10519–10531.

29. BorawskiJ, TrokeP, PuyangX, GibajaV, ZhaoS, et al. (2009) Class III phosphatidylinositol 4-kinase alpha and beta are novel host factor regulators of hepatitis C virus replication. Journal of virology 83: 10058–10074.

30. VaillancourtFH, PiloteL, CartierM, LippensJ, LiuzziM, et al. (2009) Identification of a lipid kinase as a host factor involved in hepatitis C virus RNA replication. Virology 387: 5–10.

31. HinsonER, CresswellP (2009) The antiviral protein, viperin, localizes to lipid droplets via its N-terminal amphipathic alpha-helix. Proceedings of the National Academy of Sciences of the United States of America 106: 20452–20457.

32. HelbigKJ, EyreNS, YipE, NarayanaS, LiK, et al. (2011) The antiviral protein viperin inhibits hepatitis C virus replication via interaction with nonstructural protein 5A. Hepatology 54: 1506–1517.

33. SainzBJr, BarrettoN, MartinDN, HiragaN, ImamuraM, et al. (2012) Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor. Nature medicine 18: 281–285.

34. BarrowmanJ, BhandariD, ReinischK, Ferro-NovickS (2010) TRAPP complexes in membrane traffic: convergence through a common Rab. Nature reviews Molecular cell biology 11: 759–763.

35. PileriP, UematsuY, CampagnoliS, GalliG, FalugiF, et al. (1998) Binding of hepatitis C virus to CD81. Science 282: 938–941.

36. EvansMJ, von HahnT, TscherneDM, SyderAJ, PanisM, et al. (2007) Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 446: 801–805.

37. PlossA, EvansMJ, GaysinskayaVA, PanisM, YouH, et al. (2009) Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 457: 882–886.

38. MercerJ, HeleniusA (2009) Virus entry by macropinocytosis. Nature cell biology 11: 510–520.

39. BrazzoliM, BianchiA, FilippiniS, WeinerA, ZhuQ, et al. (2008) CD81 is a central regulator of cellular events required for hepatitis C virus infection of human hepatocytes. Journal of virology 82: 8316–8329.

40. LiZ, VanceDE (2008) Phosphatidylcholine and choline homeostasis. Journal of lipid research 49: 1187–1194.

41. HaidS, PietschmannT, PecheurEI (2009) Low pH-dependent hepatitis C virus membrane fusion depends on E2 integrity, target lipid composition, and density of virus particles. The Journal of biological chemistry 284: 17657–17667.

42. BlanchardE, BelouzardS, GoueslainL, WakitaT, DubuissonJ, et al. (2006) Hepatitis C virus entry depends on clathrin-mediated endocytosis. Journal of virology 80: 6964–6972.

43. MeertensL, BertauxC, DragicT (2006) Hepatitis C virus entry requires a critical postinternalization step and delivery to early endosomes via clathrin-coated vesicles. Journal of virology 80: 11571–11578.

44. SunX, YauVK, BriggsBJ, WhittakerGR (2005) Role of clathrin-mediated endocytosis during vesicular stomatitis virus entry into host cells. Virology 338: 53–60.

45. RientoK, RidleyAJ (2003) Rocks: multifunctional kinases in cell behaviour. Nature reviews Molecular cell biology 4: 446–456.

46. GoldenbergNM, GrinsteinS, SilvermanM (2007) Golgi-bound Rab34 is a novel member of the secretory pathway. Molecular biology of the cell 18: 4762–4771.

47. CoyneCB, ShenL, TurnerJR, BergelsonJM (2007) Coxsackievirus entry across epithelial tight junctions requires occludin and the small GTPases Rab34 and Rab5. Cell host & microbe 2: 181–192.

48. TrotardM, Lepere-DouardC, RegeardM, Piquet-PellorceC, LavilletteD, et al. (2009) Kinases required in hepatitis C virus entry and replication highlighted by small interference RNA screening. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 23: 3780–3789.

49. SyedGH, AmakoY, SiddiquiA (2010) Hepatitis C virus hijacks host lipid metabolism. Trends in endocrinology and metabolism: TEM 21: 33–40.

50. DemirovD, GabrielG, SchneiderC, HohenbergH, LudwigS (2012) Interaction of influenza A virus matrix protein with RACK1 is required for virus release. Cellular microbiology 14: 774–789.

51. GallinaA, RossiF, MilanesiG (2001) Rack1 binds HIV-1 Nef and can act as a Nef-protein kinase C adaptor. Virology 283: 7–18.

52. NilssonJ, SenguptaJ, FrankJ, NissenP (2004) Regulation of eukaryotic translation by the RACK1 protein: a platform for signalling molecules on the ribosome. EMBO reports 5: 1137–1141.

53. BengaWJ, KriegerSE, DimitrovaM, ZeiselMB, ParnotM, et al. (2010) Apolipoprotein E interacts with hepatitis C virus nonstructural protein 5A and determines assembly of infectious particles. Hepatology 51: 43–53.

54. CunW, JiangJ, LuoG (2010) The C-terminal alpha-helix domain of apolipoprotein E is required for interaction with nonstructural protein 5A and assembly of hepatitis C virus. Journal of virology 84: 11532–11541.

55. HuangH, SunF, OwenDM, LiW, ChenY, et al. (2007) Hepatitis C virus production by human hepatocytes dependent on assembly and secretion of very low-density lipoproteins. Proceedings of the National Academy of Sciences of the United States of America 104: 5848–5853.

56. HerkerE, HarrisC, HernandezC, CarpentierA, KaehlckeK, et al. (2010) Efficient hepatitis C virus particle formation requires diacylglycerol acyltransferase-1. Nature medicine 16: 1295–1298.

57. LiQ, PeneV, KrishnamurthyS, ChaH, LiangTJ (2013) Hepatitis C virus infection activates an innate pathway involving IKK-alpha in lipogenesis and viral assembly. Nature medicine 19: 722–729.

58. GastaminzaP, KapadiaSB, ChisariFV (2006) Differential biophysical properties of infectious intracellular and secreted hepatitis C virus particles. Journal of virology 80: 11074–11081.

59. CollerKE, HeatonNS, BergerKL, CooperJD, SaundersJL, et al. (2012) Molecular determinants and dynamics of hepatitis C virus secretion. PLoS pathogens 8: e1002466.

60. ShintaniY, FujieH, MiyoshiH, TsutsumiT, TsukamotoK, et al. (2004) Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology 126: 840–848.

61. LiQ, AliMA, CohenJI (2006) Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread. Cell 127: 305–316.

62. TimpeJM, StamatakiZ, JenningsA, HuK, FarquharMJ, et al. (2008) Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies. Hepatology 47: 17–24.

63. MelotteV, QuX, OngenaertM, van CriekingeW, de BruineAP, et al. (2010) The N-myc downstream regulated gene (NDRG) family: diverse functions, multiple applications. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 24: 4153–4166.

64. KachhapSK, FaithD, QianDZ, ShabbeerS, GallowayNL, et al. (2007) The N-Myc down regulated Gene1 (NDRG1) Is a Rab4a effector involved in vesicular recycling of E-cadherin. PloS one 2: e844.

65. HagistS, SultmannH, MillonigG, HeblingU, KieslichD, et al. (2009) In vitro-targeted gene identification in patients with hepatitis C using a genome-wide microarray technology. Hepatology 49: 378–386.

66. KatoT, MatsumuraT, HellerT, SaitoS, SappRK, et al. (2007) Production of infectious hepatitis C virus of various genotypes in cell cultures. Journal of virology 81: 4405–4411.

67. GottweinJM, ScheelTK, JensenTB, LademannJB, PrentoeJC, et al. (2009) Development and characterization of hepatitis C virus genotype 1–7 cell culture systems: role of CD81 and scavenger receptor class B type I and effect of antiviral drugs. Hepatology 49: 364–377.

68. GottweinJM, JensenTB, MathiesenCK, MeulemanP, SerreSB, et al. (2011) Development and application of hepatitis C reporter viruses with genotype 1 to 7 core-nonstructural protein 2 (NS2) expressing fluorescent proteins or luciferase in modified JFH1 NS5A. Journal of virology 85: 8913–8928.

69. MatsumuraT, HuZ, KatoT, DreuxM, ZhangYY, et al. (2009) Amphipathic DNA polymers inhibit hepatitis C virus infection by blocking viral entry. Gastroenterology 137: 673–681.

70. LavilletteD, TarrAW, VoissetC, DonotP, BartoschB, et al. (2005) Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus. Hepatology 41: 265–274.