Dual miRNA Targeting Restricts Host Range and Attenuates Neurovirulence of Flaviviruses

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Despite advances in developing flavivirus live attenuated vaccine (LAV) candidates, a concern exists that they might not be safe in the environment due to their intrinsic genetic instability leading to potential reversion back to wild-type that could be associated with possible dissemination of these mutated viruses by mosquitoes. Here, we describe a miRNA targeting approach that can be adapted to support the design of environmentally-safe LAV restricted in their ability to infect and be transmitted by competent vectors, thereby limiting the possibility of subsequent viral evolution and unpredictable consequences. A combined co-targeting of flavivirus genome with mosquito -⁠ and vertebrate brain -⁠ specific miRNAs resulted in simultaneous restriction of dengue virus infection and replication in mosquitoes and in brains of newborn mice indicating that the miRNA-mediated approach for virus attenuation represents an alternative to non-specific strategies for the control of viral tissue tropism and pathogenesis in the vertebrate host and replicative efficacy in permissive vectors.

Vyšlo v časopise: Dual miRNA Targeting Restricts Host Range and Attenuates Neurovirulence of Flaviviruses. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004852
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004852

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Zdroje

1. Gubler DJ (1998) Resurgent vector-borne diseases as a global health problem. Emerg Infect Dis 4 : 442–450. 9716967

2. Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, et al. (2010) Dengue: a continuing global threat. Nat Rev Microbiol 8: S7–16. doi: 10.1038/nrmicro2460 21079655

3. Gubler DJ (2006) Dengue/dengue haemorrhagic fever: history and current status. Novartis Found Symp 277 : 3–16; discussion 16–22, 71–13, 251–253. 17319151

4. Ishikawa T, Yamanaka A, Konishi E (2014) A review of successful flavivirus vaccines and the problems with those flaviviruses for which vaccines are not yet available. Vaccine 32 : 1326–1337. doi: 10.1016/j.vaccine.2014.01.040 24486372

5. Schmitz J, Roehrig J, Barrett A, Hombach J (2011) Next generation dengue vaccines: a review of candidates in preclinical development. Vaccine 29 : 7276–7284. doi: 10.1016/j.vaccine.2011.07.017 21781998

6. Monath TP (2005) Yellow fever vaccine. Expert Rev Vaccines 4 : 553–574. 16117712

7. Seligman SJ, Gould EA (2004) Live flavivirus vaccines: reasons for caution. Lancet 363 : 2073–2075. 15207960

8. Hanley KA, Goddard LB, Gilmore LE, Scott TW, Speicher J, et al. (2005) Infectivity of West Nile/dengue chimeric viruses for West Nile and dengue mosquito vectors. Vector Borne Zoonotic Dis 5 : 1–10. 15815144

9. Blaney JE Jr., Sathe NS, Hanson CT, Firestone CY, Murphy BR, et al. (2007) Vaccine candidates for dengue virus type 1 (DEN1) generated by replacement of the structural genes of rDEN4 and rDEN4Delta30 with those of DEN1. Virol J 4 : 23. 17328799

10. Whitehead SS, Hanley KA, Blaney JE Jr., Gilmore LE, Elkins WR, et al. (2003) Substitution of the structural genes of dengue virus type 4 with those of type 2 results in chimeric vaccine candidates which are attenuated for mosquitoes, mice, and rhesus monkeys. Vaccine 21 : 4307–4316. 14505913

11. Blaney JE Jr., Hanson CT, Hanley KA, Murphy BR, Whitehead SS (2004) Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2. BMC Infect Dis 4 : 39. 15461822

12. Engel AR, Mitzel DN, Hanson CT, Wolfinbarger JB, Bloom ME, et al. (2011) Chimeric tick-borne encephalitis/dengue virus is attenuated in Ixodes scapularis ticks and Aedes aegypti mosquitoes. Vector Borne Zoonotic Dis 11 : 665–674. doi: 10.1089/vbz.2010.0179 21142950

13. Reid M, Mackenzie D, Baron A, Lehmann N, Lowry K, et al. (2006) Experimental infection of Culex annulirostris, Culex gelidus, and Aedes vigilax with a yellow fever/Japanese encephalitis virus vaccine chimera (ChimeriVax-JE). Am J Trop Med Hyg 75 : 659–663. 17038690

14. Bhatt TR, Crabtree MB, Guirakhoo F, Monath TP, Miller BR (2000) Growth characteristics of the chimeric Japanese encephalitis virus vaccine candidate, ChimeriVax-JE (YF/JE SA14—14—2), in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes. Am J Trop Med Hyg 62 : 480–484. 11220763

15. Johnson BW, Chambers TV, Crabtree MB, Arroyo J, Monath TP, et al. (2003) Growth characteristics of the veterinary vaccine candidate ChimeriVax-West Nile (WN) virus in Aedes and Culex mosquitoes. Med Vet Entomol 17 : 235–243. 12941006

16. Johnson BW, Chambers TV, Crabtree MB, Bhatt TR, Guirakhoo F, et al. (2002) Growth characteristics of ChimeriVax-DEN2 vaccine virus in Aedes aegypti and Aedes albopictus mosquitoes. Am J Trop Med Hyg 67 : 260–265. 12408664

17. Johnson BW, Chambers TV, Crabtree MB, Guirakhoo F, Monath TP, et al. (2004) Analysis of the replication kinetics of the ChimeriVax-DEN 1, 2, 3, 4 tetravalent virus mixture in Aedes aegypti by real-time reverse transcriptase-polymerase chain reaction. Am J Trop Med Hyg 70 : 89–97. 14971704

18. Higgs S, Vanlandingham DL, Klingler KA, McElroy KL, McGee CE, et al. (2006) Growth characteristics of ChimeriVax-Den vaccine viruses in Aedes aegypti and Aedes albopictus from Thailand. Am J Trop Med Hyg 75 : 986–993. 17124001

19. McGee CE, Tsetsarkin K, Vanlandingham DL, McElroy KL, Lang J, et al. (2008) Substitution of wild-type yellow fever Asibi sequences for 17D vaccine sequences in ChimeriVax-dengue 4 does not enhance infection of Aedes aegypti mosquitoes. J Infect Dis 197 : 686–692. doi: 10.1086/527328 18266608

20. Pedersen CE Jr., Robinson DM, Cole FE Jr. (1972) Isolation of the vaccine strain of Venezuelan equine encephalomyelitis virus from mosquitoes in Louisiana. Am J Epidemiol 95 : 490–496. 4401801

21. Simmonds P, Becher P, Collett MS, Gould EA, Heinz FX, et al. (2011) Flaviviridae. In: King AMQ, Adams MJ, Carstens EB, Lefkowitz EJ, editors. Virus Taxonomy: IXth Report of the International Committee on Taxonomy of Viruses. Oxford: Elsevier. pp. 1003–1020.

22. Kelly EJ, Russell SJ (2009) MicroRNAs and the regulation of vector tropism. Mol Ther 17 : 409–416. doi: 10.1038/mt.2008.288 19107117

23. tenOever BR (2013) RNA viruses and the host microRNA machinery. Nat Rev Microbiol 11 : 169–180. doi: 10.1038/nrmicro2971 23411862

24. Barnes D, Kunitomi M, Vignuzzi M, Saksela K, Andino R (2008) Harnessing endogenous miRNAs to control virus tissue tropism as a strategy for developing attenuated virus vaccines. Cell Host Microbe 4 : 239–248. doi: 10.1016/j.chom.2008.08.003 18779050

25. Kelly EJ, Hadac EM, Greiner S, Russell SJ (2008) Engineering microRNA responsiveness to decrease virus pathogenicity. Nat Med 14 : 1278–1283. doi: 10.1038/nm.1776 18953352

26. Cawood R, Chen HH, Carroll F, Bazan-Peregrino M, van Rooijen N, et al. (2009) Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells. PLoS Pathog 5: e1000440. doi: 10.1371/journal.ppat.1000440 19461878

27. Edge RE, Falls TJ, Brown CW, Lichty BD, Atkins H, et al. (2008) A let-7 MicroRNA-sensitive vesicular stomatitis virus demonstrates tumor-specific replication. Mol Ther 16 : 1437–1443. doi: 10.1038/mt.2008.130 18560417

28. Kelly EJ, Hadac EM, Cullen BR, Russell SJ (2010) MicroRNA antagonism of the picornaviral life cycle: alternative mechanisms of interference. PLoS Pathog 6: e1000820. doi: 10.1371/journal.ppat.1000820 20333250

29. Langlois RA, Albrecht RA, Kimble B, Sutton T, Shapiro JS, et al. (2013) MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies. Nat Biotechnol 31 : 844–847. doi: 10.1038/nbt.2666 23934176

30. Perez JT, Pham AM, Lorini MH, Chua MA, Steel J, et al. (2009) MicroRNA-mediated species-specific attenuation of influenza A virus. Nat Biotechnol 27 : 572–576. doi: 10.1038/nbt.1542 19483680

31. Ylosmaki E, Hakkarainen T, Hemminki A, Visakorpi T, Andino R, et al. (2008) Generation of a conditionally replicating adenovirus based on targeted destruction of E1A mRNA by a cell type-specific MicroRNA. J Virol 82 : 11009–11015. doi: 10.1128/JVI.01608-08 18799589

32. Ylosmaki E, Lavilla-Alonso S, Jaamaa S, Vaha-Koskela M, af Hallstrom T, et al. (2013) MicroRNA-mediated suppression of oncolytic adenovirus replication in human liver. PLoS One 8: e54506. doi: 10.1371/journal.pone.0054506 23349911

33. Ylosmaki E, Martikainen M, Hinkkanen A, Saksela K (2013) Attenuation of Semliki Forest virus neurovirulence by microRNA-mediated detargeting. J Virol 87 : 335–344. doi: 10.1128/JVI.01940-12 23077310

34. Teterina NL, Liu G, Maximova OA, Pletnev AG (2014) Silencing of neurotropic flavivirus replication in the central nervous system by combining multiple microRNA target insertions in two distinct viral genome regions. Virology 456–457 : 247–258.

35. Heiss BL, Maximova OA, Thach DC, Speicher JM, Pletnev AG (2012) MicroRNA targeting of neurotropic flavivirus: effective control of virus escape and reversion to neurovirulent phenotype. J Virol 86 : 5647–5659. doi: 10.1128/JVI.07125-11 22419812

36. Heiss BL, Maximova OA, Pletnev AG (2011) Insertion of microRNA targets into the flavivirus genome alters its highly neurovirulent phenotype. J Virol 85 : 1464–1472. doi: 10.1128/JVI.02091-10 21123372

37. Skalsky RL, Vanlandingham DL, Scholle F, Higgs S, Cullen BR (2010) Identification of microRNAs expressed in two mosquito vectors, Aedes albopictus and Culex quinquefasciatus. BMC Genomics 11 : 119. doi: 10.1186/1471-2164-11-119 20167119

38. Gu J, Hu W, Wu J, Zheng P, Chen M, et al. (2013) miRNA genes of an invasive vector mosquito, Aedes albopictus. PLoS One 8: e67638. doi: 10.1371/journal.pone.0067638 23840875

39. Bryant B, Macdonald W, Raikhel AS (2010) microRNA miR-275 is indispensable for blood digestion and egg development in the mosquito Aedes aegypti. Proc Natl Acad Sci U S A 107 : 22391–22398. doi: 10.1073/pnas.1016230107 21115818

40. Durbin AP, Karron RA, Sun W, Vaughn DW, Reynolds MJ, et al. (2001) Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3'-untranslated region. Am J Trop Med Hyg 65 : 405–413. 11716091

41. Blaney JE Jr., Manipon GG, Firestone CY, Johnson DH, Hanson CT, et al. (2003) Mutations which enhance the replication of dengue virus type 4 and an antigenic chimeric dengue virus type 2/4 vaccine candidate in Vero cells. Vaccine 21 : 4317–4327. 14505914

42. Engel AR, Rumyantsev AA, Maximova OA, Speicher JM, Heiss B, et al. (2010) The neurovirulence and neuroinvasiveness of chimeric tick-borne encephalitis/dengue virus can be attenuated by introducing defined mutations into the envelope and NS5 protein genes and the 3' non-coding region of the genome. Virology 405 : 243–252. doi: 10.1016/j.virol.2010.06.014 20594569

43. Rumyantsev AA, Chanock RM, Murphy BR, Pletnev AG (2006) Comparison of live and inactivated tick-borne encephalitis virus vaccines for safety, immunogenicity and efficacy in rhesus monkeys. Vaccine 24 : 133–143. 16115704

44. Blaney JE Jr., Speicher J, Hanson CT, Sathe NS, Whitehead SS, et al. (2008) Evaluation of St. Louis encephalitis virus/dengue virus type 4 antigenic chimeric viruses in mice and rhesus monkeys. Vaccine 26 : 4150–4159. doi: 10.1016/j.vaccine.2008.05.075 18586359

45. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136 : 215–233. doi: 10.1016/j.cell.2009.01.002 19167326

46. Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9 : 102–114. doi: 10.1038/nrg2290 18197166

47. Bonaldo MC, Mello SM, Trindade GF, Rangel AA, Duarte AS, et al. (2007) Construction and characterization of recombinant flaviviruses bearing insertions between E and NS1 genes. Virol J 4 : 115. 17971212

48. Pletnev AG, Putnak R, Speicher J, Wagar EJ, Vaughn DW (2002) West Nile virus/dengue type 4 virus chimeras that are reduced in neurovirulence and peripheral virulence without loss of immunogenicity or protective efficacy. Proc Natl Acad Sci U S A 99 : 3036–3041. 11880643

49. McElroy KL, Tsetsarkin KA, Vanlandingham DL, Higgs S (2006) Manipulation of the yellow fever virus non-structural genes 2A and 4B and the 3'non-coding region to evaluate genetic determinants of viral dissemination from the Aedes aegypti midgut. Am J Trop Med Hyg 75 : 1158–1164. 17172386

50. McElroy KL, Tsetsarkin KA, Vanlandingham DL, Higgs S (2006) Role of the yellow fever virus structural protein genes in viral dissemination from the Aedes aegypti mosquito midgut. J Gen Virol 87 : 2993–3001. 16963758

51. Jennings AD, Gibson CA, Miller BR, Mathews JH, Mitchell CJ, et al. (1994) Analysis of a yellow fever virus isolated from a fatal case of vaccine-associated human encephalitis. J Infect Dis 169 : 512–518. 7908925

52. L. W (1939) Failure of Aedes aegypti to transmit yellow fever cultured virus (17D). Am J Trop Med Hyg 19 : 19–26.

53. Troyer JM, Hanley KA, Whitehead SS, Strickman D, Karron RA, et al. (2001) A live attenuated recombinant dengue-4 virus vaccine candidate with restricted capacity for dissemination in mosquitoes and lack of transmission from vaccinees to mosquitoes. Am J Trop Med Hyg 65 : 414–419. 11716092

54. Pham AM, Langlois RA, TenOever BR (2012) Replication in cells of hematopoietic origin is necessary for Dengue virus dissemination. PLoS Pathog 8: e1002465. doi: 10.1371/journal.ppat.1002465 22241991

55. Pasquinelli AE (2012) MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship. Nat Rev Genet 13 : 271–282. doi: 10.1038/nrg3162 22411466

56. Saetrom P, Heale BS, Snove O Jr., Aagaard L, Alluin J, et al. (2007) Distance constraints between microRNA target sites dictate efficacy and cooperativity. Nucleic Acids Res 35 : 2333–2342. 17389647

57. Lee YS, Nakahara K, Pham JW, Kim K, He Z, et al. (2004) Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways. Cell 117 : 69–81. 15066283

58. Brackney DE, Scott JC, Sagawa F, Woodward JE, Miller NA, et al. (2010) C6/36 Aedes albopictus cells have a dysfunctional antiviral RNA interference response. PLoS Negl Trop Dis 4: e856. doi: 10.1371/journal.pntd.0000856 21049065

59. Scott JC, Brackney DE, Campbell CL, Bondu-Hawkins V, Hjelle B, et al. (2010) Comparison of dengue virus type 2-specific small RNAs from RNA interference-competent and-incompetent mosquito cells. PLoS Negl Trop Dis 4: e848. doi: 10.1371/journal.pntd.0000848 21049014

60. Gu S, Jin L, Zhang F, Sarnow P, Kay MA (2009) Biological basis for restriction of microRNA targets to the 3' untranslated region in mammalian mRNAs. Nat Struct Mol Biol 16 : 144–150. doi: 10.1038/nsmb.1552 19182800

61. Grimson A, Farh KK, Johnston WK, Garrett-Engele P, Lim LP, et al. (2007) MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 27 : 91–105. 17612493

62. Ameres SL, Martinez J, Schroeder R (2007) Molecular basis for target RNA recognition and cleavage by human RISC. Cell 130 : 101–112. 17632058

63. Herfst S, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E, et al. (2012) Airborne transmission of influenza A/H5N1 virus between ferrets. Science 336 : 1534–1541. doi: 10.1126/science.1213362 22723413

64. Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, et al. (2012) Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature 486 : 420–428. doi: 10.1038/nature10831 22722205

65. Linster M, van Boheemen S, de Graaf M, Schrauwen EJ, Lexmond P, et al. (2014) Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus. Cell 157 : 329–339. doi: 10.1016/j.cell.2014.02.040 24725402

66. Bredenbeek PJ, Kooi EA, Lindenbach B, Huijkman N, Rice CM, et al. (2003) A stable full-length yellow fever virus cDNA clone and the role of conserved RNA elements in flavivirus replication. J Gen Virol 84 : 1261–1268. 12692292

67. Sambrook J, Fritsch E, Maniatis T (1989) Molecular Cloning: a Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.

68. Vanlandingham DL, McGee CE, Klinger KA, Vessey N, Fredregillo C, et al. (2007) Relative susceptibilties of South Texas mosquitoes to infection with West Nile virus. Am J Trop Med Hyg 77 : 925–928. 17984355

69. Pilitt DR, Jones JC (1972) A qualitative method for estimating the degree of engorgement of Aedes aegypti adults. J Med Entomol 9 : 334–337. 5054499

70. Pall GS, Hamilton AJ (2008) Improved northern blot method for enhanced detection of small RNA. Nat Protoc 3 : 1077–1084. doi: 10.1038/nprot.2008.67 18536652