Programmed Ribosomal Frameshift Alters Expression of West Nile Virus Genes and Facilitates Virus Replication in Birds and Mosquitoes

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Programmed ribosomal frameshift (PRF) is a strategy used by some viruses to regulate expression of viral genes and/or generate additional gene products for the benefit of the virus. Encephalitic flaviruses from Japanese encephalitis virus serogroup encode PRF motif in the beginning of nonstructural gene NS2A that results in production of an additional nonstructural protein NS1′ which for West Nile virus (WNV) consists of NS1 protein with 52 amino acid addition at the C terminus. Our previous studies showed that abolishing PFR and NS1′ production attenuated WNV virulence in mice. Here we show by using wild type and PRF-deficient WNV mutant that PRF induces overproduction of structural proteins, which facilitates virus replication in birds and mosquitoes while having no advantage for virus replication in cell lines in vitro. Presence of PRF/NS1′ allowed more efficient virus dissemination in the body of mosquitoes after taking infected blood meal and subsequent accumulation of the virus in saliva to facilitate transmission. Combined with our previous data in mice, the results obtained in this study demonstrate that while having no advantage for WNV replication in vitro, PRF provides advantage for WNV replication in vivo in mammalian, avian and mosquito hosts most likely by overproducing viral structural proteins and generating NS1′.

Vyšlo v časopise: Programmed Ribosomal Frameshift Alters Expression of West Nile Virus Genes and Facilitates Virus Replication in Birds and Mosquitoes. PLoS Pathog 10(11): e32767. doi:10.1371/journal.ppat.1004447
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004447

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Zdroje

1. Diamond MS (2009) West Nile Encephalitis Virus Infection; I.W F, editor. New York: Springer. 485 p.

2. ZhangY, KaufmannB, ChipmanPR, KuhnRJ, RossmannMG (2007) Structure of immature West Nile virus. J Virol 81: 6141–6145.

3. MackenzieJM, JonesMK, YoungPR (1996) Immunolocalization of the dengue virus nonstructural glycoprotein NS1 suggests a role in viral RNA replication. Virology 220: 232–240.

4. MackenzieJM, KhromykhAA, JonesMK, WestawayEG (1998) Subcellular localization and some biochemical properties of the flavivirus Kunjin nonstructural proteins NS2A and NS4A. Virology 245: 203–215.

5. KhromykhAA, SedlakPL, WestawayEG (2000) cis- and trans-acting elements in flavivirus RNA replication. J Virol 74: 3253–3263.

6. YounS, LiT, McCuneBT, EdelingMA, FremontDH, et al. (2012) Evidence for a genetic and physical interaction between nonstructural proteins NS1 and NS4B that modulates replication of West Nile virus. J Virol 86: 7360–7371.

7. RossiSL, FayzulinR, DewsburyN, BourneN, MasonPW (2007) Mutations in West Nile virus nonstructural proteins that facilitate replicon persistence in vitro attenuate virus replication in vitro and in vivo. Virology 364: 184–195.

8. YamshchikovVF, CompansRW (1994) Processing of the intracellular form of the west Nile virus capsid protein by the viral NS2B-NS3 protease: an in vitro study. J Virol 68: 5765–5771.

9. RoosendaalJ, WestawayEG, KhromykhA, MackenzieJM (2006) Regulated cleavages at the West Nile virus NS4A-2K-NS4B junctions play a major role in rearranging cytoplasmic membranes and Golgi trafficking of the NS4A protein. J Virol 80: 4623–4632.

10. ChernovAV, ShiryaevSA, AleshinAE, RatnikovBI, SmithJW, et al. (2008) The two-component NS2B-NS3 proteinase represses DNA unwinding activity of the West Nile virus NS3 helicase. J Biol Chem 283: 17270–17278.

11. LeungJY, PijlmanGP, KondratievaN, HydeJ, MackenzieJM, et al. (2008) Role of nonstructural protein NS2A in flavivirus assembly. J Virol 82: 4731–4741.

12. KummererBM, RiceCM (2002) Mutations in the yellow fever virus nonstructural protein NS2A selectively block production of infectious particles. J Virol 76: 4773–4784.

13. LiuWJ, WangXJ, ClarkDC, LobigsM, HallRA, et al. (2006) A single amino acid substitution in the West Nile virus nonstructural protein NS2A disables its ability to inhibit alpha/beta interferon induction and attenuates virus virulence in mice. J Virol 80: 2396–2404.

14. AshourJ, Laurent-RolleM, ShiPY, Garcia-SastreA (2009) NS5 of dengue virus mediates STAT2 binding and degradation. J Virol 83: 5408–5418.

15. Laurent-RolleM, BoerEF, LubickKJ, WolfinbargerJB, CarmodyAB, et al. (2010) The NS5 protein of the virulent West Nile virus NY99 strain is a potent antagonist of type I interferon-mediated JAK-STAT signaling. J Virol 84: 3503–3515.

16. WermeK, WigeriusM, JohanssonM (2008) Tick-borne encephalitis virus NS5 associates with membrane protein scribble and impairs interferon-stimulated JAK-STAT signalling. Cell Microbiol 10: 696–712.

17. LinRJ, ChangBL, YuHP, LiaoCL, LinYL (2006) Blocking of interferon-induced Jak-Stat signaling by Japanese encephalitis virus NS5 through a protein tyrosine phosphatase-mediated mechanism. J Virol 80: 5908–5918.

18. BestSM, MorrisKL, ShannonJG, RobertsonSJ, MitzelDN, et al. (2005) Inhibition of interferon-stimulated JAK-STAT signaling by a tick-borne flavivirus and identification of NS5 as an interferon antagonist. J Virol 79: 12828–12839.

19. WilsonJR, de SessionsPF, LeonMA, ScholleF (2008) West Nile virus nonstructural protein 1 inhibits TLR3 signal transduction. J Virol 82: 8262–8271.

20. ChungKM, LiszewskiMK, NybakkenG, DavisAE, TownsendRR, et al. (2006) West Nile virus nonstructural protein NS1 inhibits complement activation by binding the regulatory protein factor H. Proc Natl Acad Sci U S A 103: 19111–19116.

21. MasonPW (1989) Maturation of Japanese encephalitis virus glycoproteins produced by infected mammalian and mosquito cells. Virology 169: 354–364.

22. FirthAE, AtkinsJF (2009) A conserved predicted pseudoknot in the NS2A-encoding sequence of West Nile and Japanese encephalitis flaviviruses suggests NS1′ may derive from ribosomal frameshifting. Virol J 6: 14.

23. MelianEB, HinzmanE, NagasakiT, FirthAE, WillsNM, et al. (2010) NS1′ of flaviviruses in the Japanese encephalitis virus serogroup is a product of ribosomal frameshifting and plays a role in viral neuroinvasiveness. J Virol 84: 1641–1647.

24. SunJ, YuY, DeubelV (2012) Japanese encephalitis virus NS1′ protein depends on pseudoknot secondary structure and is cleaved by caspase during virus infection and cell apoptosis. Microbes Infect 14: 930–940.

25. TakamatsuY, OkamotoK, DinhDT, YuF, HayasakaD, et al. (2014) NS1′ protein expression facilitates production of Japanese encephalitis virus in avian cells and embryonated chicken eggs. J Gen Virol 95: 373–383.

26. WinkelmannER, WidmanDG, SuzukiR, MasonPW (2011) Analyses of mutations selected by passaging a chimeric flavivirus identify mutations that alter infectivity and reveal an interaction between the structural proteins and the nonstructural glycoprotein NS1. Virology 421: 96–104.

27. YoungLB, MelianEB, KhromykhAA (2013) NS1′ co-localizes with NS1 and can substitute for NS1 in West Nile virus replication. J Virol 87: 9384–9390.

28. YeQ, LiXF, ZhaoH, LiSH, DengYQ, et al. (2012) A single nucleotide mutation in NS2A of Japanese encephalitis-live vaccine virus (SA14-14-2) ablates NS1′ formation and contributes to attenuation. J Gen Virol 93: 1959–1964.

29. YounS, AmbroseRL, MackenzieJM, DiamondMS (2013) Non-structural protein-1 is required for West Nile virus replication complex formation and viral RNA synthesis. Virol J 10: 339.

30. MelianEB, EdmondsJH, NagasakiTK, HinzmanE, FlodenN, et al. (2013) West Nile virus NS2A protein facilitates virus-induced apoptosis independently of interferon response. J Gen Virol 94: 308–313.

31. TurellMJ, O'GuinnML, JonesJW, SardelisMR, DohmDJ, et al. (2005) Isolation of viruses from mosquitoes (Diptera: Culicidae) collected in the Amazon Basin region of Peru. J Med Entomol 42: 891–898.

32. BraultAC, LangevinSA, BowenRA, PanellaNA, BiggerstaffBJ, et al. (2004) Differential virulence of West Nile strains for American crows. Emerg Infect Dis 10: 2161–2168.

33. LangevinSA, BraultAC, PanellaNA, BowenRA, KomarN (2005) Variation in virulence of West Nile virus strains for house sparrows (Passer domesticus). Am J Trop Med Hyg 72: 99–102.

34. LiuWJ, ChenHB, WangXJ, HuangH, KhromykhAA (2004) Analysis of adaptive mutations in Kunjin virus replicon RNA reveals a novel role for the flavivirus nonstructural protein NS2A in inhibition of beta interferon promoter-driven transcription. J Virol 78: 12225–12235.

35. LiSH, LiXF, ZhaoH, DengYQ, YuXD, et al. (2013) Development and characterization of the replicon system of Japanese encephalitis live vaccine virus SA14-14-2. Virol J 10: 64.

36. MackenzieJM, WestawayEG (2001) Assembly and maturation of the flavivirus Kunjin virus appear to occur in the rough endoplasmic reticulum and along the secretory pathway, respectively. J Virol 75: 10787–10799.

37. BraultAC, LangevinSA, RameyWN, FangY, BeasleyDW, et al. (2011) Reduced avian virulence and viremia of West Nile virus isolates from Mexico and Texas. Am J Trop Med Hyg 85: 758–767.

38. LangevinSA, BowenRA, RameyWN, SandersTA, MaharajPD, et al. (2011) Envelope and pre-membrane protein structural amino acid mutations mediate diminished avian growth and virulence of a Mexican West Nile virus isolate. J Gen Virol 92: 2810–2820.

39. LangevinSA, BowenRA, ReisenWK, AndradeCC, RameyWN, et al. (2014) Host Competence and Helicase Activity Differences Exhibited by West Nile Viral Variants Expressing NS3-249 Amino Acid Polymorphisms. PLoS ONE 9: e100802.

40. DuggalN, Bosco-LauthA, BowenR, WheelerS, ReisenW, et al. (2014) Evidence for co-evolution of West Nile virus and house sparrows in North America. PLoS Negl Trop Dis 8: e3262.

41. BrierleyI, JennerAJ, InglisSC (1992) Mutational analysis of the “slippery-sequence” component of a coronavirus ribosomal frameshifting signal. J Mol Biol 227: 463–479.

42. BrierleyI, PennellS, GilbertRJ (2007) Viral RNA pseudoknots: versatile motifs in gene expression and replication. Nat Rev Microbiol 5: 598–610.

43. Shehu-XhilagaM, CroweSM, MakJ (2001) Maintenance of the Gag/Gag-Pol ratio is important for human immunodeficiency virus type 1 RNA dimerization and viral infectivity. J Virol 75: 1834–1841.

44. ZhaiY, SunF, LiX, PangH, XuX, et al. (2005) Insights into SARS-CoV transcription and replication from the structure of the nsp7-nsp8 hexadecamer. Nat Struct Mol Biol 12: 980–986.

45. ImbertI, GuillemotJC, BourhisJM, BussettaC, CoutardB, et al. (2006) A second, non-canonical RNA-dependent RNA polymerase in SARS coronavirus. EMBO J 25: 4933–4942.

46. DaffisS, SutharMS, SzretterKJ, GaleMJr, DiamondMS (2009) Induction of IFN-beta and the innate antiviral response in myeloid cells occurs through an IPS-1-dependent signal that does not require IRF-3 and IRF-7. PLoS Pathog 5: e1000607.

47. PeskoKN, EbelGD (2012) West Nile virus population genetics and evolution. Infect Genet Evol 12: 181–190.

48. DingSW (2010) RNA-based antiviral immunity. Nat Rev Immunol 10: 632–644.

49. WuQ, WangX, DingSW (2010) Viral suppressors of RNA-based viral immunity: host targets. Cell Host Microbe 8: 12–15.

50. ArjonaA, WangP, MontgomeryRR, FikrigE (2011) Innate immune control of West Nile virus infection. Cell Microbiol 13: 1648–1658.

51. BrackneyDE, ScottJC, SagawaF, WoodwardJE, MillerNA, et al. (2010) C6/36 Aedes albopictus cells have a dysfunctional antiviral RNA interference response. PLoS Negl Trop Dis 4: e856.

52. TurellMJ, GarganTP2nd, BaileyCL (1984) Replication and dissemination of Rift Valley fever virus in Culex pipiens. Am J Trop Med Hyg 33: 176–181.

53. DavisMM, EngstromY (2012) Immune response in the barrier epithelia: lessons from the fruit fly Drosophila melanogaster. J Innate Immun 4: 273–283.

54. Tchankouo-NguetcheuS, KhunH, PincetL, RouxP, BahutM, et al. (2010) Differential protein modulation in midguts of Aedes aegypti infected with chikungunya and dengue 2 viruses. PLoS One 5: e13149.

55. AudsleyM, EdmondsJ, LiuW, MokhonovV, MokhonovaE, et al. (2011) Virulence determinants between New York 99 and Kunjin strains of West Nile virus. Virology 414: 63–73.

56. AdamsSC, BroomAK, SammelsLM, HartnettAC, HowardMJ, et al. (1995) Glycosylation and antigenic variation among Kunjin virus isolates. Virology 206: 49–56.

57. LinSM, DuP, HuberW, KibbeWA (2008) Model-based variance-stabilizing transformation for Illumina microarray data. Nucleic Acids Res 36: e11.

58. BenjaminiY, HochbergY (1995) Controlling the False Discovery Rate - a Practical and Powerful Approach to Multiple Testing. J R Stat Soc Series B-Methodol 57: 289–300.

59. JohnsonPH, Hall-MendelinS, WhelanPI, FrancesSP, JansenCC, et al. (2009) Vector competence of Australian Culex gelidus Theobald (Diptera: Culicidae) for endemic and exotic arboviruses. Aust J Entomol 48: 234–240.

60. WellsPJ, ValeTG, RussellRC, CloonanMJ (1994) Comparison of a pledget technique with other methods for bloodfeeding mosquitoes (Diptera: Culicidae) for virus studies. J Aust Entomol Soc 33: 211–212.

61. van den HurkAF, Hall-MendelinS, PykeAT, FrentiuFD, McElroyK, et al. (2012) Impact of Wolbachia on infection with chikungunya and yellow fever viruses in the mosquito vector Aedes aegypti. PLoS Negl Trop Dis 6: e1892.

62. BroomAK, HallRA, JohansenCA, OliveiraN, HowardMA, et al. (1998) Identification of Australian arboviruses in inoculated cell cultures using monoclonal antibodies in ELISA. Pathology 30: 286–288.