Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles

English version České info

In vitro systems have been developed for the study of hepatitis C virus (HCV) infection and have revealed many details of the life cycle of HCV. Apolipoprotein B (ApoB) and ApoE have been shown to play crucial roles in the particle formation of HCV, based on data obtained by siRNA-mediated gene knockdown and overexpression of the proteins. However, precise roles of the apolipoproteins in HCV assembly have not been elucidated yet. In this study, we show that infectious particle formation of HCV in Huh7 cells was severely impaired by the knockout of both ApoB and ApoE genes by artificial nucleases, and this reduction was cancelled by the expression of not only ApoE, but also other exchangeable apolipoproteins, including ApoA1, ApoA2, ApoC1, ApoC2 and ApoC3. In addition, expression of amphipathic α-helices in the exchangeable apolipoproteins restored the infectious particle formation in the double-knockout cells through an interaction with viral particles. These results provide clues to the understanding of life cycle of HCV and the development of novel antivirals to HCV.

Vyšlo v časopise: Amphipathic α-Helices in Apolipoproteins Are Crucial to the Formation of Infectious Hepatitis C Virus Particles. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004534
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004534

Souhrn

Zdroje

1. MaasoumyB, WedemeyerH (2012) Natural history of acute and chronic hepatitis C. Best. Pract. Res. Clin. 26: 410–412.

2. JacobsonIM, McHutchisonJG, DusheikoG, Di BisceglieAM, ReddyKR, et al. (2011) Telaprevir for previously untreated chronic hepatitis C virus infection. N. Engl. J. Med. 364: 2405–2416.

3. SulkowskiMS, GardinerDF, Rodriguez-TorresM, ReddyKR, HassaneinT, et al. (2014) Daclatasvir plus Sofosbuvir for previously treated or untreated chronic HCV infection. N. Engl. J. Med. 370: 211–221.

4. JanssenHL, ReesinkHW, LawitzEJ, ZeuzemS, Rodriguez-TorresM, et al. (2013) Treatment of HCV infection by targeting microRNA. N. Engl. J. Med. 368: 1685–1694.

5. BartoschB, DubuissonJ, CossetF (2003) Infectious hepatitis C virus pseudo-particles containing functional E1–E2 envelope protein complexes. J. Exp. Med. 197: 633–642.

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

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

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

9. JiraskoV, MontserretR, LeeJY, GouttenoireJ, MoradpourD, et al. (2010) Structural and functional studies of nonstructural protein 2 of the hepatitis C virus reveal its key role as organizer of virion assembly. PLoS Pathog 6: e1001233.

10. GastaminzaP, ChengG, WielandS, ZhongJ, LiaoW, et al. (2008) Cellular determinants of hepatitis C virus assembly, maturation, degradation, and secretion. J. Virol. 82: 2120–2129.

11. JiangJ, LuoG (2009) Apolipoprotein E but not B is required for the formation of infectious hepatitis C virus particles. J. Virol. 83: 12680–12691.

12. AndreP, Komurian-PradelF, DeforgesS, PerretM, BerlandL, et al. (2002) Characterization of Low- and Very-Low-Density hepatitis C virus RNA-containing particles. J. Virol. 76: 6919–6928.

13. SaitoH, Lund-KatzS, PhillipsMC (2004) Contribution of domain structure and lipid interaction to the functionality of exchangeable human apolipoproteins. Prog. Lipid Res. 43: 350–380.

14. NarayanaswamiV, KissRS, WeersPM (2010) The helix bundle: A reversible lipid binding motif. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 155: 123–133.

15. ManconeC, SteindlerC, SantangeloL, SimonteG, VlassiC, et al. (2011) Hepatitis C virus production requires apolipoprotein A-1 and affects its association with nascent low-density lipoproteins. Gut. 60: 378–386.

16. Da CostaD, TurekM, FelmeeDJ, GirardiE, PfefferS, et al. (2012) Reconstitution of the entire hepatitis C virus life cycle in nonhepatic cells. J. Virol. 86: 11919–11925.

17. PorteusMH, CarrollD (2005) Gene targeting using zinc finger nucleases. Nat. Biotechnol. 23: 967–973.

18. ZhangF, CongL, LodatoS, KosuriS, ChurchGM, et al. (2011) Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription. Nat. Biotechnol. 29: 149–153.

19. MaliP, YangL, EsveltKM, AachJ, GuellM, et al. (2013) RNA-guided human genome engineering via Cas9. Science 339: 823–826.

20. KupershmidtI, SuQJ, GrewalA, SundareshS, HalperinI, et al. (2010) Ontology-based meta-analysis of global collections of high-throughput public data. PLoS One 5: e13066.

21. HussainMM, ShiJ, DreizenP (2003) Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly. J. Lipid Res. 44: 22–32.

22. TakebeY, SaucedoCJ, LundG, UenishiR, HaseS, et al. (2013) Antiviral lectins from Red and Blue-Green Algae show potent in vitro and in vivo activity against hepatitis C virus. PLoS One 8: e64449.

23. KimS, DateT, YokokawaH, KonoT, AizakiH, et al. (2014) Development of hepatitis C virus genotype 3a cell culture system. Hepatology doi:10.1002/hep.27197

24. MiyanariY, AtsuzawaK, UsudaN, WatashiK, HishikiT, et al. (2007) The lipid droplet is an important organelle for hepatitis C virus production. Nat. Cell Biol. 9: 961–969.

25. BosonB, GranioO, BartenschlagerR, CossetF (2011) A concerted action of hepatitis C virus p7 and nonstructural protein 2 regulates core localization at the endoplasmic reticulum and virus assembly. PLoS Pathog. 7: e1002144.

26. GentzschJ, BrohmC, SteinmannE, FrieslandM, MenzelN, et al. (2013) Hepatitis C virus p7 is critical for capsid assembly and envelopment. PLoS Pathog. 9: e1003355.

27. ShavinskayaA, BoulantS, PeninF, McLauchlanJ, BartenschlagerR (2007) The lipid droplet binding domain of hepatitis C virus core protein is a major determinant for efficient virus assembly. J. Biol. Chem. 282: 37158–37169.

28. AiL, LeeY, ChenSS (2009) Characterization of hepatitis C virus core protein multimerization and membrane envelopment: revelation of a cascade of core-membrane interactions. J. Virol. 83: 9923–9939.

29. MeiX, AtkinsonD (2011) Crystal structure of C-terminal truncated apolipoprotein A-1 reveals the assembly of high density lipoprotein (HDL) by dimerization. J. Biol. Chem. 286: 38570–38582.

30. RozekA, SparrowJT, WeisgraberKH, CushleyJR (1999) Conformation of human apolipoprotein C-1 in a lipid-mimetic environment determined by CD and NMR spectrometry. Biochemistry 38: 14475–14484.

31. EichingerA, NasreenA, JinH (2007) Structural insight into the dual ligand specificity and mode of high density lipoprotein association of apolipoprotein D. J. Biol. Chem. 282: 31068–31075.

32. ChenJ, LiQ, WangJ (2011) Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions. Proc. Natl. Acad. Sci. U. S. A. 108: 14813–14818.

33. SchwarzenbacherR, ZethK, DiederichsK, GriesA, KostnerGM, et al. (1999) Crystal structure of human β2-glycoprotein 1: implication for phospholipid binding and the antiphospholipid syndrome. EMBO J. 18: 6228–6239.

34. SevvanaM, KasslerK, AhnstromJ, WeilerS, DahlbackB, et al. (2010) Mouse ApoM displays an unprecedented seven-stranded lipocalin fold: folding decoy or alternative native fold? J. Mol. Biol. 404: 363–371.

35. NielsenSU, BassendineMF, BurtAD, MartinC, PumeechockchaiW, et al. (2006) Association between hepatitis C virus and very-low-density lipoprotein (VLDL)/LDL analyzed in iodixanol density gradients. J. Virol. 80: 2418–2428.

36. JammartB, MicheletM, PecheurE, ParentR, BartoschB, et al. (2013) Very-low-density lipoprotein (VLDL)-prpducing and hepatitis C virus-replicating HepG2 cells secrete no more lipoviroparticles than VLDL-deficient Huh7.5 cells. J. Virol. 87: 1405–1412.

37. HuegingK, DoepkeM, VieyresG, BankwitzD, FrentzenA, et al. (2014) Apolipoprotein E codetermines tissue tropism of hepatitis C virus and is crucial for viral cell-to-cell transmission by contributing to a postenvelopment step of assembly. J. Virol. 88: 1433–1466.

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

39. CataneseTM, UryuK, KoppM, EdwardsTJ, AndrusL, et al. (2013) Ultrastructural analysis of hepatitis C virus particles. Proc. Natl. Acad. Sci. U. S. A. 110: 9505–9510.

40. ChengG, MonteroA, GastaminzaP, Whitten-BauerC, WielandSF, et al. (2008) A virocidal amphipathic α-helical peptide that inhibits hepatitis C virus infection in vitro. Proc. Natl. Acad. Sci. U. S. A. 105: 3088–3093.

41. ScarselliE, AnsuiniH, CerinoR, RoccaseccaRM, AcaliS, et al. (2002) The human scavenger receptor class B type 1 is a novel candidate receptor for the hepatitis C virus. EMBO J. 21: 5017–5025.

42. MolinaS, CastetV, Fournier-WirthC, Pichard-GarciaL, AvnerR, et al. (2007) The low-density lipoprotein receptor plays a role in the infection of primary human hepatocytes by hepatitis C virus. J. Hepatol. 46: 411–419.

43. OwenDM, HuangH, YeJ, GaleMJ (2009) Apolipoprotein E on hepatitis C virion facilitates infection through interaction with low-density lipoprotein receptor. Virology 394: 99–108.

44. PrentoeJ, SerreSB, RamirezS, NicosiaA, GottweinJM, et al. (2014) Hypervariable region 1 deletion and required adaptive envelope mutations confer decreased dependency on scavenger receptor class B type 1 and low density lipoprotein receptor for hepatitis C virus. J. Virol. 88: 1725–1739.

45. MeunierJ, RussellRS, EngleRE, FaulkKN, PurcellRH, et al. (2008) Apolipoprotein C1 association with hepatitis C virus. J. Virol. 82: 9647–9656.

46. DreuxM, BosonB, Ricard-BlumS, MolleJ, LavilletteD, et al. (2007) The exchangeable apolipoprotein ApoC-1 promotes membrane fusion of hepatitis C virus. J. Biol. Chem. 282: 32357–32369.

47. FukuharaT, MatsuuraY (2013) Role of miR-122 and lipid metabolism in HCV infection. J. Gastroenterol. 48: 169–176.

48. 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.

49. MercerDF, SchillerDE, ElliottJF, DouglasDN, HaoC, et al. (2001) Hepatitis C virus replication in mice with chimeric human livers. Nat. Med. 7: 927–933.

50. DornerM, HorwitzJA, DonovanBM, LabittRN, BudellBC, et al. (2013) Completion of the entire hepatitis C virus life cycle in genetically humanized mice. Nature 501: 237–241.

51. WangH, YangH, ShivalilaCS, DawlatyMM, ChengAW, et al. (2013) One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153: 910–918.

52. ChoSW, KimS, KimJM, KimJ (2013) Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat. Biotechnol. 31: 230–232.

53. ShalemO, SanjanaNE, HartenianE, ShiX, ScottDA, et al. (2014) Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343: 84–87.

54. FukuharaT, KambaraH, ShiokawaM, OnoC, KatohH, et al. (2012) Expression of microRNA miR-122 facilitates an efficient replication in nonhepatic cells upon infection with hepatitis C virus. J. Virol. 86: 7918–7933.

55. RussellRS, MeunierJC, TakikawaS, FaulkK, EngleRE, et al. (2008) Advantages of a single-cycle production assay to study cell culture-adaptive mutations of hepatitis C virus. Proc. Natl. Acad. Sci. U. S. A. 105: 4370–4375

56. GuschinYD, WaiteAJ, KatibahGE, MillerJC, HolmesMC, et al. (2010) A rapid and general assay for monitoring endogenous gene modification. Methods Mol. Biol. 649: 247–256 (2010).

57. RiederCL, BowserSS (1985) Correlative immunofluorescence and electron microscopy on the same section of epon-embedded material. J. Histochem. Cytochem. 33: 165–171.