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preLekára.sk / Odborné časopisy / PLOS Pathogens / 2015 - 3

Spatiotemporal Analysis of Hepatitis C Virus Infection

English version České info

The stages of the viral life cycle are spatially and temporally regulated to coordinate the infectious process in a way that maximizes successful replication and spread. In this study, we used RNA in situ hybridization (ISH) to simultaneously detect HCV (+) and (−) RNAs and analyze the kinetics of HCV infection at the single cell level as well as visualize HCV RNAs associated with actively translating ribosomes, markers of viral replication compartment formation, active RNA replication, nucleocapsid assembly, and intracellular virions. We observed a spatial linkage between sites of viral translation and replication, in addition to replication and assembly. HCV (+) RNAs follow a tight temporal regulation. They are initially associated with translating ribosomes, followed by a peak of replication that achieves a steady state level. The remaining HCV (+) RNAs are then devoted to virion assembly. Analysis of HCV (−) RNAs revealed that low levels of transient RNA replication occur early after infection prior to the formation of devoted replication compartments and robust replication. This suggests that HCV synthesizes additional (+) and (−) strands early in infection, likely to decrease its reliance on maintaining the integrity of the initially infecting (+) RNA.

Vyšlo v časopise: Spatiotemporal Analysis of Hepatitis C Virus Infection. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004758
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004758

Souhrn

The stages of the viral life cycle are spatially and temporally regulated to coordinate the infectious process in a way that maximizes successful replication and spread. In this study, we used RNA in situ hybridization (ISH) to simultaneously detect HCV (+) and (−) RNAs and analyze the kinetics of HCV infection at the single cell level as well as visualize HCV RNAs associated with actively translating ribosomes, markers of viral replication compartment formation, active RNA replication, nucleocapsid assembly, and intracellular virions. We observed a spatial linkage between sites of viral translation and replication, in addition to replication and assembly. HCV (+) RNAs follow a tight temporal regulation. They are initially associated with translating ribosomes, followed by a peak of replication that achieves a steady state level. The remaining HCV (+) RNAs are then devoted to virion assembly. Analysis of HCV (−) RNAs revealed that low levels of transient RNA replication occur early after infection prior to the formation of devoted replication compartments and robust replication. This suggests that HCV synthesizes additional (+) and (−) strands early in infection, likely to decrease its reliance on maintaining the integrity of the initially infecting (+) RNA.

Zdroje

1. Choo QL, Richman KH, Han JH, Berger K, Lee C, et al. (1991) Genetic organization and diversity of the hepatitis C virus. Proc Natl Acad Sci U S A 88: 2451–2455. 1848704

2. Grakoui A, Wychowski C, Lin C, Feinstone SM, Rice CM (1993) Expression and identification of hepatitis C virus polyprotein cleavage products. J Virol 67: 1385–1395. 7679746

3. Lohmann V, Korner F, Koch J, Herian U, Theilmann L, et al. (1999) Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285: 110–113. 10390360

4. Blight KJ, Kolykhalov AA, Rice CM (2000) Efficient initiation of HCV RNA replication in cell culture. Science 290: 1972–1974. 11110665

5. Egger D, Wolk B, Gosert R, Bianchi L, Blum HE, et al. (2002) Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J Virol 76: 5974–5984. 12021330

6. Moradpour D, Gosert R, Egger D, Penin F, Blum HE, et al. (2003) Membrane association of hepatitis C virus nonstructural proteins and identification of the membrane alteration that harbors the viral replication complex. Antiviral Res 60: 103–109. 14638405

7. Gosert R, Egger D, Lohmann V, Bartenschlager R, Blum HE, et al. (2003) Identification of the hepatitis C virus RNA replication complex in Huh-7 cells harboring subgenomic replicons. J Virol 77: 5487–5492. 12692249

8. Kato H, Takahasi K, Fujita T (2011) RIG-I-like receptors: cytoplasmic sensors for non-self RNA. Immunol Rev 243: 91–98. doi: 10.1111/j.1600-065X.2011.01052.x 21884169

9. Romero-Brey I, Merz A, Chiramel A, Lee JY, Chlanda P, et al. (2012) Three-dimensional architecture and biogenesis of membrane structures associated with hepatitis C virus replication. PLoS Pathog 8: e1003056. doi: 10.1371/journal.ppat.1003056 23236278

10. Behrens SE, Tomei L, De Francesco R (1996) Identification and properties of the RNA-dependent RNA polymerase of hepatitis C virus. EMBO J 15: 12–22. 8598194

11. Lohmann V, Korner F, Herian U, Bartenschlager R (1997) Biochemical properties of hepatitis C virus NS5B RNA-dependent RNA polymerase and identification of amino acid sequence motifs essential for enzymatic activity. J Virol 71: 8416–8428. 9343198

12. Miyanari Y, Atsuzawa K, Usuda N, Watashi K, Hishiki T, et al. (2007) The lipid droplet is an important organelle for hepatitis C virus production. Nat Cell Biol 9: 1089–1097. 17721513

13. Gamarnik AV, Andino R (1998) Switch from translation to RNA replication in a positive-stranded RNA virus. Genes Dev 12: 2293–2304. 9694795

14. Oakland TE, Haselton KJ, Randall G (2013) EWSR1 binds the hepatitis C virus cis-acting replication element and is required for efficient viral replication. J Virol 87: 6625–6634. doi: 10.1128/JVI.01006-12 23552423

15. Perera R, Daijogo S, Walter BL, Nguyen JH, Semler BL (2007) Cellular protein modification by poliovirus: the two faces of poly(rC)-binding protein. J Virol 81: 8919–8932. 17581994

16. Evans MJ, Rice CM, Goff SP (2004) Phosphorylation of hepatitis C virus nonstructural protein 5A modulates its protein interactions and viral RNA replication. Proc Natl Acad Sci U S A 101: 13038–13043. 15326295

17. Dahari H, Major M, Zhang X, Mihalik K, Rice CM, et al. (2005) Mathematical modeling of primary hepatitis C infection: noncytolytic clearance and early blockage of virion production. Gastroenterology 128: 1056–1066. 15825086

18. Dahari H, Feliu A, Garcia-Retortillo M, Forns X, Neumann AU (2005) Second hepatitis C replication compartment indicated by viral dynamics during liver transplantation. J Hepatol 42: 491–498. 15763335

19. Powers KA, Ribeiro RM, Patel K, Pianko S, Nyberg L, et al. (2006) Kinetics of hepatitis C virus reinfection after liver transplantation. Liver Transpl 12: 207–216. 16447184

20. Dahari H, Sainz B Jr., Perelson AS, Uprichard SL (2009) Modeling subgenomic hepatitis C virus RNA kinetics during treatment with alpha interferon. J Virol 83: 6383–6390. doi: 10.1128/JVI.02612-08 19369346

21. Dixit NM, Layden-Almer JE, Layden TJ, Perelson AS (2004) Modelling how ribavirin improves interferon response rates in hepatitis C virus infection. Nature 432: 922–924. 15602565

22. Dahari H, Ribeiro RM, Rice CM, Perelson AS (2007) Mathematical modeling of subgenomic hepatitis C virus replication in Huh-7 cells. J Virol 81: 750–760. 17035310

23. Mishchenko EL, Bezmaternykh KD, Likhoshvai VA, Ratushny AV, Khlebodarova TM, et al. (2007) Mathematical model for suppression of subgenomic hepatitis C virus RNA replication in cell culture. J Bioinform Comput Biol 5: 593–609. 17636864

24. McLean AK, Luciani F, Tanaka MM (2010) Trade-offs in resource allocation in the intracellular life-cycle of hepatitis C virus. J Theor Biol 267: 565–572. doi: 10.1016/j.jtbi.2010.09.031 20883700

25. Binder M, Sulaimanov N, Clausznitzer D, Schulze M, Huber CM, et al. (2013) Replication vesicles are load- and choke-points in the hepatitis C virus lifecycle. PLoS Pathog 9: e1003561. doi: 10.1371/journal.ppat.1003561 23990783

26. Keum SJ, Park SM, Park JH, Jung JH, Shin EJ, et al. (2012) The specific infectivity of hepatitis C virus changes through its life cycle. Virology 433: 462–470. doi: 10.1016/j.virol.2012.08.046 22999258

27. Player AN, Shen LP, Kenny D, Antao VP, Kolberg JA (2001) Single-copy gene detection using branched DNA (bDNA) in situ hybridization. J Histochem Cytochem 49: 603–612. 11304798

28. Dreux M, Garaigorta U, Boyd B, Decembre E, Chung J, 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. doi: 10.1016/j.chom.2012.08.010 23084922

29. Wieland S, Makowska Z, Campana B, Calabrese D, Dill MT, et al. (2014) Simultaneous detection of hepatitis C virus and interferon stimulated gene expression in infected human liver. Hepatology 59: 2121–2130. doi: 10.1002/hep.26770 24122862

30. Sofia MJ, Bao D, Chang W, Du J, Nagarathnam D, et al. (2010) Discovery of a beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus. J Med Chem 53: 7202–7218. doi: 10.1021/jm100863x 20845908

31. Stedman C (2014) Sofosbuvir, a NS5B polymerase inhibitor in the treatment of hepatitis C: a review of its clinical potential. Therap Adv Gastroenterol 7: 131–140. doi: 10.1177/1756283X13515825 24790644

32. Gao M, Nettles RE, Belema M, Snyder LB, Nguyen VN, et al. (2010) Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect. Nature 465: 96–100. doi: 10.1038/nature08960 20410884

33. Au JS, Pockros PJ (2014) Novel therapeutic approaches for hepatitis C. Clin Pharmacol Ther 95: 78–88. doi: 10.1038/clpt.2013.206 24126682

34. Chang M, Williams O, Mittler J, Quintanilla A, Carithers RL Jr., et al. (2003) Dynamics of hepatitis C virus replication in human liver. Am J Pathol 163: 433–444. 12875965

35. Quinkert D, Bartenschlager R, Lohmann V (2005) Quantitative analysis of the hepatitis C virus replication complex. J Virol 79: 13594–13605. 16227280

36. David A, Dolan BP, Hickman HD, Knowlton JJ, Clavarino G, et al. (2012) Nuclear translation visualized by ribosome-bound nascent chain puromycylation. J Cell Biol 197: 45–57. doi: 10.1083/jcb.201112145 22472439

37. Targett-Adams P, Boulant S, McLauchlan J (2008) Visualization of double-stranded RNA in cells supporting hepatitis C virus RNA replication. J Virol 82: 2182–2195. 18094154

38. Appel N, Zayas M, Miller S, Krijnse-Locker J, Schaller T, et al. (2008) Essential role of domain III of nonstructural protein 5A for hepatitis C virus infectious particle assembly. PLoS Pathog 4: e1000035. doi: 10.1371/journal.ppat.1000035 18369481

39. Penin F, Brass V, Appel N, Ramboarina S, Montserret R, et al. (2004) Structure and function of the membrane anchor domain of hepatitis C virus nonstructural protein 5A. J Biol Chem 279: 40835–40843. 15247283

40. Lohmann V, Hoffmann S, Herian U, Penin F, Bartenschlager R (2003) Viral and cellular determinants of hepatitis C virus RNA replication in cell culture. J Virol 77: 3007–3019. 12584326

41. Berger KL, Cooper JD, Heaton NS, Yoon R, Oakland TE, et al. (2009) Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replication. Proc Natl Acad Sci U S A 106: 7577–7582. doi: 10.1073/pnas.0902693106 19376974

42. Reiss S, Rebhan I, Backes P, Romero-Brey I, Erfle H, 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. doi: 10.1016/j.chom.2010.12.002 21238945

43. Tai AW, Salloum S (2011) The role of the phosphatidylinositol 4-kinase PI4KA in hepatitis C virus-induced host membrane rearrangement. PLoS One 6: e26300. doi: 10.1371/journal.pone.0026300 22022594

44. Lam AM, Frick DN (2006) Hepatitis C virus subgenomic replicon requires an active NS3 RNA helicase. J Virol 80: 404–411. 16352565

45. Ma Y, Yates J, Liang Y, Lemon SM, Yi M (2008) NS3 helicase domains involved in infectious intracellular hepatitis C virus particle assembly. J Virol 82: 7624–7639. doi: 10.1128/JVI.00724-08 18508894

46. Boulant S, Targett-Adams P, McLauchlan J (2007) Disrupting the association of hepatitis C virus core protein with lipid droplets correlates with a loss in production of infectious virus. J Gen Virol 88: 2204–2213. 17622624

47. Shavinskaya A, Boulant S, Penin F, McLauchlan J, Bartenschlager R (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. 17942391

48. Coller KE, Heaton NS, Berger KL, Cooper JD, Saunders JL, et al. (2012) Molecular determinants and dynamics of hepatitis C virus secretion. PLoS Pathog 8: e1002466. doi: 10.1371/journal.ppat.1002466 22241992

49. Counihan NA, Rawlinson SM, Lindenbach BD (2011) Trafficking of hepatitis C virus core protein during virus particle assembly. PLoS Pathog 7: e1002302. doi: 10.1371/journal.ppat.1002302 22028650

50. Nielsen SU, Bassendine MF, Burt AD, Martin C, Pumeechockchai W, 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. 16474148

51. Hadlock KG, Lanford RE, Perkins S, Rowe J, Yang Q, et al. (2000) Human monoclonal antibodies that inhibit binding of hepatitis C virus E2 protein to CD81 and recognize conserved conformational epitopes. J Virol 74: 10407–10416. 11044085

52. Jirasko V, Montserret R, Lee JY, Gouttenoire J, Moradpour D, 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. doi: 10.1371/journal.ppat.1001233 21187906

53. Garaigorta U, Heim MH, Boyd B, Wieland S, Chisari FV (2012) Hepatitis C virus (HCV) induces formation of stress granules whose proteins regulate HCV RNA replication and virus assembly and egress. J Virol 86: 11043–11056. 22855484

54. Appel N, Herian U, Bartenschlager R (2005) Efficient rescue of hepatitis C virus RNA replication by trans-complementation with nonstructural protein 5A. J Virol 79: 896–909. 15613318

55. Liu HM, Aizaki H, Machida K, Ou JH, Lai MM (2012) Hepatitis C virus translation preferentially depends on active RNA replication. PLoS One 7: e43600. doi: 10.1371/journal.pone.0043600 22937067

56. Heaton NS, Perera R, Berger KL, Khadka S, Lacount DJ, et al. (2010) Dengue virus nonstructural protein 3 redistributes fatty acid synthase to sites of viral replication and increases cellular fatty acid synthesis. Proc Natl Acad Sci U S A 107: 17345–17350. doi: 10.1073/pnas.1010811107 20855599

57. Boson B, Granio O, Bartenschlager R, Cosset FL (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. doi: 10.1371/journal.ppat.1002144 21814513

58. Blight KJ, McKeating JA, Rice CM (2002) Highly permissive cell lines for subgenomic and genomic hepatitis C virus RNA replication. J Virol 76: 13001–13014. 12438626

59. Mateu G, Donis RO, Wakita T, Bukh J, Grakoui A (2008) Intragenotypic JFH1 based recombinant hepatitis C virus produces high levels of infectious particles but causes increased cell death. Virology 376: 397–407. doi: 10.1016/j.virol.2008.03.027 18455749

60. Pietschmann T, Kaul A, Koutsoudakis G, Shavinskaya A, Kallis S, et al. (2006) Construction and characterization of infectious intragenotypic and intergenotypic hepatitis C virus chimeras. Proc Natl Acad Sci U S A 103: 7408–7413. 16651538

61. Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, et al. (2005) Complete replication of hepatitis C virus in cell culture. Science 309: 623–626. 15947137

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