Exosomes from Hepatitis C Infected Patients Transmit HCV Infection and Contain Replication Competent Viral RNA in Complex with Ago2-miR122-HSP90
Since its first isolation and identification in 1989, Hepatitis C virus (HCV), has caused significant disease burden to humans worldwide. So far, there is no vaccine against HCV, and neutralizing antibody therapies to block receptor–mediated transmission of HCV to liver cells have so far achieved limited therapeutic benefits. This indicates that HCV can transmit infection via receptor-independent mechanisms. Evidence suggests that small host extracellular vesicles (exosomes) can mediate receptor-independent transfer of genetic material between cells, though their role in HCV transmission remains uncertain. Here, we found that the HCV virus can utilize host exosomes to transmit infection to naïve liver cells, even in the presence of potent blocking anti-HCV receptor antibody treatments. Additionally, we identified alternative treatment strategies that can block host exosomes from transmitting HCV infection. Our study provides novel insights to an alternative mechanism of HCV transmission that can compromise anti-HCV immune therapies and proposes potential therapeutic approaches to block exosome-mediated transmission of HCV infection.
Vyšlo v časopise:
Exosomes from Hepatitis C Infected Patients Transmit HCV Infection and Contain Replication Competent Viral RNA in Complex with Ago2-miR122-HSP90. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004424
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004424
Souhrn
Since its first isolation and identification in 1989, Hepatitis C virus (HCV), has caused significant disease burden to humans worldwide. So far, there is no vaccine against HCV, and neutralizing antibody therapies to block receptor–mediated transmission of HCV to liver cells have so far achieved limited therapeutic benefits. This indicates that HCV can transmit infection via receptor-independent mechanisms. Evidence suggests that small host extracellular vesicles (exosomes) can mediate receptor-independent transfer of genetic material between cells, though their role in HCV transmission remains uncertain. Here, we found that the HCV virus can utilize host exosomes to transmit infection to naïve liver cells, even in the presence of potent blocking anti-HCV receptor antibody treatments. Additionally, we identified alternative treatment strategies that can block host exosomes from transmitting HCV infection. Our study provides novel insights to an alternative mechanism of HCV transmission that can compromise anti-HCV immune therapies and proposes potential therapeutic approaches to block exosome-mediated transmission of HCV infection.
Zdroje
1. ShepardCW, FinelliL, AlterMJ (2005) Global epidemiology of hepatitis C virus infection. The Lancet infectious diseases 5: 558–567.
2. NegroF, AlbertiA (2011) The global health burden of hepatitis C virus infection. Liver international : official journal of the International Association for the Study of the Liver 31 Suppl 2: 1–3.
3. ScheelTK, RiceCM (2013) Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nature medicine 19: 837–849.
4. RubinA, AguileraV, BerenguerM (2011) Liver transplantation and hepatitis C. Clinics and research in hepatology and gastroenterology 35: 805–812.
5. FormanLM (2003) To transplant or not to transplant recurrent hepatitis C and liver failure. Clinics in liver disease 7: 615–629.
6. 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.
7. MorinTJ, BroeringTJ, LeavBA, BlairBM, RowleyKJ, et al. (2012) Human monoclonal antibody HCV1 effectively prevents and treats HCV infection in chimpanzees. PLoS pathogens 8: e1002895.
8. GottweinJM, BukhJ (2008) Cutting the gordian knot-development and biological relevance of hepatitis C virus cell culture systems. Advances in virus research 71: 51–133.
9. ZeiselMB, FofanaI, Fafi-KremerS, BaumertTF (2011) Hepatitis C virus entry into hepatocytes: molecular mechanisms and targets for antiviral therapies. Journal of hepatology 54: 566–576.
10. ScarselliE, AnsuiniH, CerinoR, RoccaseccaRM, AcaliS, et al. (2002) The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. The EMBO journal 21: 5017–5025.
11. PileriP, UematsuY, CampagnoliS, GalliG, FalugiF, et al. (1998) Binding of hepatitis C virus to CD81. Science 282: 938–941.
12. MeulemanP, HesselgesserJ, PaulsonM, VanwolleghemT, DesombereI, et al. (2008) Anti-CD81 antibodies can prevent a hepatitis C virus infection in vivo. Hepatology 48: 1761–1768.
13. DavisGL (2006) Hepatitis C immune globulin to prevent HCV recurrence after liver transplantation: chasing windmills? Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 12: 1317–1319.
14. ManciniN, DiottiRA, PerottiM, SauttoG, ClementiN, et al. (2009) Hepatitis C virus (HCV) infection may elicit neutralizing antibodies targeting epitopes conserved in all viral genotypes. PloS one 4: e8254.
15. SchianoTD, CharltonM, YounossiZ, GalunE, PruettT, et al. (2006) Monoclonal antibody HCV-AbXTL68 in patients undergoing liver transplantation for HCV: results of a phase 2 randomized study. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 12: 1381–1389.
16. WitteveldtJ, EvansMJ, BitzegeioJ, KoutsoudakisG, OwsiankaAM, et al. (2009) CD81 is dispensable for hepatitis C virus cell-to-cell transmission in hepatoma cells. The Journal of general virology 90: 48–58.
17. LeeY, El AndaloussiS, WoodMJ (2012) Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Human molecular genetics 21: R125–134.
18. TheryC, ZitvogelL, AmigorenaS (2002) Exosomes: composition, biogenesis and function. Nature reviews Immunology 2: 569–579.
19. Momen-HeraviF, BalajL, AlianS, TiggesJ, ToxavidisV, et al. (2012) Alternative methods for characterization of extracellular vesicles. Frontiers in physiology 3: 354.
20. YangM, ChenJ, SuF, YuB, SuF, et al. (2011) Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Molecular cancer 10: 117.
21. PietschmannT, LohmannV, KaulA, KriegerN, RinckG, et al. (2002) Persistent and transient replication of full-length hepatitis C virus genomes in cell culture. Journal of virology 76: 4008–4021.
22. GastaminzaP, DrydenKA, BoydB, WoodMR, LawM, et al. (2010) Ultrastructural and biophysical characterization of hepatitis C virus particles produced in cell culture. Journal of virology 84: 10999–11009.
23. MasciopintoF, GiovaniC, CampagnoliS, Galli-StampinoL, ColombattoP, et al. (2004) Association of hepatitis C virus envelope proteins with exosomes. European journal of immunology 34: 2834–2842.
24. DreuxM, GaraigortaU, BoydB, DecembreE, ChungJ, et al. (2012) Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity. Cell Host Microbe 12: 558–570.
25. 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.
26. WilsonJA, ZhangC, HuysA, RichardsonCD (2011) Human Ago2 is required for efficient microRNA 122 regulation of hepatitis C virus RNA accumulation and translation. Journal of virology 85: 2342–2350.
27. HenkeJI, GoergenD, ZhengJ, SongY, SchuttlerCG, et al. (2008) microRNA-122 stimulates translation of hepatitis C virus RNA. The EMBO journal 27: 3300–3310.
28. JoplingCL, SchutzS, SarnowP (2008) Position-dependent function for a tandem microRNA miR-122-binding site located in the hepatitis C virus RNA genome. Cell host & microbe 4: 77–85.
29. JoplingCL, YiM, LancasterAM, LemonSM, SarnowP (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309: 1577–1581.
30. JangraRK, YiM, LemonSM (2010) Regulation of hepatitis C virus translation and infectious virus production by the microRNA miR-122. Journal of virology 84: 6615–6625.
31. BukongTN, HouW, KodysK, SzaboG (2013) Ethanol facilitates hepatitis C virus replication via up-regulation of GW182 and heat shock protein 90 in human hepatoma cells. Hepatology 57: 70–80.
32. WileyRD, GummuluruS (2006) Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection. Proceedings of the National Academy of Sciences of the United States of America 103: 738–743.
33. RiceCM (2011) New insights into HCV replication: potential antiviral targets. Topics in antiviral medicine 19: 117–120.
34. BroeringTJ, GarrityKA, BoatrightNK, SloanSE, SandorF, et al. (2009) Identification and characterization of broadly neutralizing human monoclonal antibodies directed against the E2 envelope glycoprotein of hepatitis C virus. Journal of virology 83: 12473–12482.
35. AkazawaD, DateT, MorikawaK, MurayamaA, MiyamotoM, et al. (2007) CD81 expression is important for the permissiveness of Huh7 cell clones for heterogeneous hepatitis C virus infection. Journal of virology 81: 5036–5045.
36. 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.
37. BukongTN, HouW, KodysK, SzaboG (2012) Ethanol facilitates HCV replication via upregulation of GW182 and HSP90 in human hepatoma cells. Hepatology 10.1002/hep.26010.
38. ShimakamiT, YamaneD, JangraRK, KempfBJ, SpanielC, et al. (2012) Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proceedings of the National Academy of Sciences of the United States of America 109: 941–946.
39. ShimakamiT, YamaneD, JangraRK, KempfBJ, SpanielC, et al. (2012) Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex. Proceedings of the National Academy of Sciences of the United States of America 109: 941–946.
40. UjinoS, YamaguchiS, ShimotohnoK, TakakuH (2009) Heat-shock protein 90 is essential for stabilization of the hepatitis C virus nonstructural protein NS3. J Biol Chem 284: 6841–6846.
41. TscherneDM, JonesCT, EvansMJ, LindenbachBD, McKeatingJA, et al. (2006) Time- and temperature-dependent activation of hepatitis C virus for low-pH-triggered entry. Journal of virology 80: 1734–1741.
42. 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.
43. ParoliniI, FedericiC, RaggiC, LuginiL, PalleschiS, et al. (2009) Microenvironmental pH is a key factor for exosome traffic in tumor cells. The Journal of biological chemistry 284: 34211–34222.
44. SimonsM, RaposoG (2009) Exosomes–vesicular carriers for intercellular communication. Current opinion in cell biology 21: 575–581.
45. Momen-HeraviF, BalajL, AlianS, MantelPY, HalleckAE, et al. (2013) Current methods for the isolation of extracellular vesicles. Biological chemistry 10.1515/hsz-2013-0141.
46. SilvermanJM, ReinerNE (2011) Exosomes and other microvesicles in infection biology: organelles with unanticipated phenotypes. Cellular microbiology 13: 1–9.
47. BhatnagarS, ShinagawaK, CastellinoFJ, SchoreyJS (2007) Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo. Blood 110: 3234–3244.
48. RamakrishnaiahV, ThumannC, FofanaI, HabersetzerF, PanQ, et al. (2013) Exosome-mediated transmission of hepatitis C virus between human hepatoma Huh7.5 cells. Proceedings of the National Academy of Sciences of the United States of America 110: 13109–13113.
49. BlightKJ, McKeatingJA, RiceCM (2002) Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication. Journal of virology 76: 13001–13014.
50. HaoJ, JinW, LiX, WangS, ZhangX, et al. (2013) Inhibition of alpha interferon (IFN-alpha)-induced microRNA-122 negatively affects the anti-hepatitis B virus efficiency of IFN-alpha. J Virol 87: 137–147.
51. Sarasin-FilipowiczM, KrolJ, MarkiewiczI, HeimMH, FilipowiczW (2009) Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nature medicine 15: 31–33.
52. JohnstonM, GeoffroyMC, SobalaA, HayR, HutvagnerG (2010) HSP90 protein stabilizes unloaded argonaute complexes and microscopic P-bodies in human cells. Molecular biology of the cell 21: 1462–1469.
53. OkamotoT, NishimuraY, IchimuraT, SuzukiK, MiyamuraT, et al. (2006) Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90. The EMBO journal 25: 5015–5025.
54. UjinoS, YamaguchiS, ShimotohnoK, TakakuH (2009) Heat-shock protein 90 is essential for stabilization of the hepatitis C virus nonstructural protein NS3. J Biol Chem 284: 6841–6846.
55. TheryC, ZitvogelL, AmigorenaS (2002) Exosomes: composition, biogenesis and function. Nature reviews Immunology 2: 569–579.
56. DenzerK, KleijmeerMJ, HeijnenHF, StoorvogelW, GeuzeHJ (2000) Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. Journal of cell science 113 Pt 19: 3365–3374.
57. SobotaJA, BackN, EipperBA, MainsRE (2009) Inhibitors of the V0 subunit of the vacuolar H+-ATPase prevent segregation of lysosomal- and secretory-pathway proteins. Journal of cell science 122: 3542–3553.
58. Alvarez-ErvitiL, SeowY, SchapiraAH, GardinerC, SargentIL, et al. (2011) Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiology of disease 42: 360–367.
59. VingtdeuxV, HamdaneM, LoyensA, GeleP, DrobeckH, et al. (2007) Alkalizing drugs induce accumulation of amyloid precursor protein by-products in luminal vesicles of multivesicular bodies. The Journal of biological chemistry 282: 18197–18205.
60. BlanchardE, BelouzardS, GoueslainL, WakitaT, DubuissonJ, et al. (2006) Hepatitis C virus entry depends on clathrin-mediated endocytosis. Journal of virology 80: 6964–6972.
61. LimJH, ParkJW, KimMS, ParkSK, JohnsonRS, et al. (2006) Bafilomycin induces the p21-mediated growth inhibition of cancer cells under hypoxic conditions by expressing hypoxia-inducible factor-1alpha. Molecular pharmacology 70: 1856–1865.
62. LindenbachBD, EvansMJ, SyderAJ, WolkB, TellinghuisenTL, et al. (2005) Complete replication of hepatitis C virus in cell culture. Science 309: 623–626.
63. BalaS, PetrasekJ, MundkurS, CatalanoD, LevinI, et al. (2012) Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 56: 1946–1957.
64. ItoT, MukaigawaJ, ZuoJ, HirabayashiY, MitamuraK, et al. (1996) Cultivation of hepatitis C virus in primary hepatocyte culture from patients with chronic hepatitis C results in release of high titre infectious virus. The Journal of general virology 77 (Pt 5) 1043–1054.
65. BukongTN, KodysK, SzaboG (2013) Human ezrin-moesin-radixin proteins modulate hepatitis C virus infection. Hepatology 58: 1569–1579.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2014 Číslo 10
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Novel Cyclic di-GMP Effectors of the YajQ Protein Family Control Bacterial Virulence
- MicroRNAs Suppress NB Domain Genes in Tomato That Confer Resistance to
- CD4 Depletion in SIV-Infected Macaques Results in Macrophage and Microglia Infection with Rapid Turnover of Infected Cells
- Theory and Empiricism in Virulence Evolution