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Dengue Virus RNA Structure Specialization Facilitates Host Adaptation


Important viral pathogens, such as influenza and dengue, jump between species; however, it is still unclear how these viruses evolved for efficient replication in significantly different environments. Using dengue virus as a model, which naturally alternates between humans and mosquitoes, changes in the viral RNA were investigated in each host. Deep sequencing analysis revealed the selection of strikingly different viral populations during host adaptation. Fitness measurements indicated that mutations in a single RNA structure of the viral 3’ untranslated region were responsible for positive and negative selection of specific viral variants in the two hosts. Cycles of disruption and reconstitution of this RNA structure were observed during host switching, identifying a host adaptable RNA element. Importantly, natural duplication of this RNA was found to be required to tolerate mosquito-associated mutations for efficient replication in mammalian cells. Our studies revealed a novel strategy of viral adaptation, where RNA structure specialization and duplication provide a mechanism for maintaining high viral fitness in each host and efficiency during host cycling. Because the identified RNA structure and its duplication are conserved in many mosquito-borne flaviviruses, our findings using dengue virus could help to understand RNA evolution of an extensive group of human pathogens.


Vyšlo v časopise: Dengue Virus RNA Structure Specialization Facilitates Host Adaptation. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004604
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004604

Souhrn

Important viral pathogens, such as influenza and dengue, jump between species; however, it is still unclear how these viruses evolved for efficient replication in significantly different environments. Using dengue virus as a model, which naturally alternates between humans and mosquitoes, changes in the viral RNA were investigated in each host. Deep sequencing analysis revealed the selection of strikingly different viral populations during host adaptation. Fitness measurements indicated that mutations in a single RNA structure of the viral 3’ untranslated region were responsible for positive and negative selection of specific viral variants in the two hosts. Cycles of disruption and reconstitution of this RNA structure were observed during host switching, identifying a host adaptable RNA element. Importantly, natural duplication of this RNA was found to be required to tolerate mosquito-associated mutations for efficient replication in mammalian cells. Our studies revealed a novel strategy of viral adaptation, where RNA structure specialization and duplication provide a mechanism for maintaining high viral fitness in each host and efficiency during host cycling. Because the identified RNA structure and its duplication are conserved in many mosquito-borne flaviviruses, our findings using dengue virus could help to understand RNA evolution of an extensive group of human pathogens.


Zdroje

1. Steinhauer DA, Domingo E, Holland JJ (1992) Lack of evidence for proofreading mechanisms associated with an RNA virus polymerase. Gene 122: 281–288. doi: 10.1016/0378-1119(92)90216-C 1336756

2. Borderia AV, Stapleford KA, Vignuzzi M (2011) RNA virus population diversity: implications for inter-species transmission. Curr Opin Virol 1: 643–648. doi: 10.1016/j.coviro.2011.09.012 22440922

3. Domingo E, Holland JJ (1997) RNA virus mutations and fitness for survival. Annu Rev Microbiol 51: 151–178. doi: 10.1146/annurev.micro.51.1.151 9343347

4. Jenkins GM, Rambaut A, Pybus OG, Holmes EC (2002) Rates of molecular evolution in RNA viruses: a quantitative phylogenetic analysis. J Mol Evol 54: 156–165. doi: 10.1007/s00239-001-0064-3 11821909

5. Woolhouse ME, Taylor LH, Haydon DT (2001) Population biology of multihost pathogens. Science 292: 1109–1112. doi: 10.1126/science.1059026 11352066

6. Ciota AT, Kramer LD (2010) Insights into arbovirus evolution and adaptation from experimental studies. Viruses 2: 2594–2617. doi: 10.3390/v2122594 21994633

7. Coffey LL, Forrester N, Tsetsarkin K, Vasilakis N, Weaver SC (2013) Factors shaping the adaptive landscape for arboviruses: implications for the emergence of disease. Future Microbiol 8: 155–176. doi: 10.2217/fmb.12.139 23374123

8. Villordo SM, Gamarnik AV (2013) Differential RNA sequence requirement for dengue virus replication in mosquito and mammalian cells. J Virol 87: 9365–9372. doi: 10.1128/JVI.00567-13 23760236

9. Gebhard LG, Filomatori CV, Gamarnik AV (2011) Functional RNA elements in the dengue virus genome. Viruses 3: 1739–1756. doi: 10.3390/v3091739 21994804

10. Filomatori CV, Lodeiro MF, Alvarez DE, Samsa MM, Pietrasanta L, et al. (2006) A 5' RNA element promotes dengue virus RNA synthesis on a circular genome. Genes Dev 20: 2238–2249. doi: 10.1101/gad.1444206 16882970

11. Gritsun TS, Gould EA (2006) Direct repeats in the 3' untranslated regions of mosquito-borne flaviviruses: possible implications for virus transmission. J Gen Virol 87: 3297–3305. doi: 10.1099/vir.0.82235-0 17030864

12. Gritsun TS, Gould EA (2007) Origin and evolution of 3'UTR of flaviviruses: long direct repeats as a basis for the formation of secondary structures and their significance for virus transmission. Adv Virus Res 69: 203–248. doi: 10.1016/S0065-3527(06)69005-2 17222695

13. Kinney RM, Butrapet S, Chang GJ, Tsuchiya KR, Roehrig JT, et al. (1997) Construction of infectious cDNA clones for dengue 2 virus: strain 16681 and its attenuated vaccine derivative, strain PDK-53. Virology 230: 300–308. doi: 10.1006/viro.1997.8500 9143286

14. Vodovar N, Bronkhorst AW, van Cleef KW, Miesen P, Blanc H, et al. (2012) Arbovirus-derived piRNAs exhibit a ping-pong signature in mosquito cells. PLoS One 7: e30861. doi: 10.1371/journal.pone.0030861 22292064

15. Manzano M, Reichert ED, Polo S, Falgout B, Kasprzak W, et al. (2011) Identification of cis-acting elements in the 3'-untranslated region of the dengue virus type 2 RNA that modulate translation and replication. J Biol Chem 286: 22521–22534. doi: 10.1074/jbc.M111.234302 21515677

16. Sztuba-Solinska J, Teramoto T, Rausch JW, Shapiro BA, Padmanabhan R, et al. (2013) Structural complexity of Dengue virus untranslated regions: cis-acting RNA motifs and pseudoknot interactions modulating functionality of the viral genome. Nucleic Acids Res 41: 5075–5089. doi: 10.1093/nar/gkt203 23531545

17. Pijlman GP, Funk A, Kondratieva N, Leung J, Torres S, et al. (2008) A highly structured, nuclease-resistant, noncoding RNA produced by flaviviruses is required for pathogenicity. Cell Host Microbe 4: 579–591. doi: 10.1016/j.chom.2008.10.007 19064258

18. Chapman EG, Moon SL, Wilusz J, Kieft JS (2014) RNA structures that resist degradation by Xrn1 produce a pathogenic Dengue virus RNA. Elife 3: e01892. doi: 10.7554/eLife.01892 24692447

19. Samsa MM, Mondotte JA, Caramelo JJ, Gamarnik AV (2012) Uncoupling cis-Acting RNA elements from coding sequences revealed a requirement of the N-terminal region of dengue virus capsid protein in virus particle formation. J Virol 86: 1046–1058. doi: 10.1128/JVI.05431-11 22072762

20. Schnettler E, Tykalova H, Watson M, Sharma M, Sterken MG, et al. (2014) Induction and suppression of tick cell antiviral RNAi responses by tick-borne flaviviruses. Nucleic Acids Res 42: 9436–9446. doi: 10.1093/nar/gku657 25053841

21. Hussain M, Torres S, Schnettler E, Funk A, Grundhoff A, et al. (2012) West Nile virus encodes a microRNA-like small RNA in the 3' untranslated region which up-regulates GATA4 mRNA and facilitates virus replication in mosquito cells. Nucleic Acids Res 40: 2210–2223. doi: 10.1093/nar/gkr848 22080551

22. Hussain M, Asgari S (2014) MicroRNA-like viral small RNA from Dengue virus 2 autoregulates its replication in mosquito cells. Proc Natl Acad Sci U S A 111: 2746–2751. doi: 10.1073/pnas.1320123111 24550303

23. Ward AM, Bidet K, Yinglin A, Ler SG, Hogue K, et al. (2011) Quantitative mass spectrometry of DENV-2 RNA-interacting proteins reveals that the DEAD-box RNA helicase DDX6 binds the DB1 and DB2 3' UTR structures. RNA Biol 8: 1173–1186. doi: 10.4161/rna.8.6.17836 21957497

24. Bidet K, Dadlani D, Garcia-Blanco MA (2014) G3BP1, G3BP2 and CAPRIN1 are required for translation of interferon stimulated mRNAs and are targeted by a dengue virus non-coding RNA. PLoS Pathog 10: e1004242. doi: 10.1371/journal.ppat.1004242 24992036

25. Chapman EG, Costantino DA, Rabe JL, Moon SL, Wilusz J, et al. (2014) The structural basis of pathogenic subgenomic flavivirus RNA (sfRNA) production. Science 344: 307–310. doi: 10.1126/science.1250897 24744377

26. Daffis S, Lazear HM, Liu WJ, Audsley M, Engle M, et al. (2011) The naturally attenuated Kunjin strain of West Nile virus shows enhanced sensitivity to the host type I interferon response. J Virol 85: 5664–5668. doi: 10.1128/JVI.00232-11 21411525

27. Schnettler E, Sterken MG, Leung JY, Metz SW, Geertsema C, et al. (2012) Noncoding flavivirus RNA displays RNA interference suppressor activity in insect and Mammalian cells. J Virol 86: 13486–13500. doi: 10.1128/JVI.01104-12 23035235

28. Alvarez DE, De Lella Ezcurra AL, Fucito S, Gamarnik AV (2005) Role of RNA structures present at the 3'UTR of dengue virus on translation, RNA synthesis, and viral replication. Virology 339: 200–212. doi: 10.1016/j.virol.2005.06.009 16002117

29. Tajima S, Nukui Y, Takasaki T, Kurane I (2007) Characterization of the variable region in the 3' non-translated region of dengue type 1 virus. J Gen Virol 88: 2214–2222. doi: 10.1099/vir.0.82661-0 17622625

30. Tumban E, Mitzel DN, Maes NE, Hanson CT, Whitehead SS, et al. (2011) Replacement of the 3' untranslated variable region of mosquito-borne dengue virus with that of tick-borne Langat virus does not alter vector specificity. J Gen Virol 92: 841–848. doi: 10.1099/vir.0.026997-0 21216984

31. Vasilakis N, Deardorff ER, Kenney JL, Rossi SL, Hanley KA, et al. (2009) Mosquitoes put the brake on arbovirus evolution: experimental evolution reveals slower mutation accumulation in mosquito than vertebrate cells. PLoS Pathog 5: e1000467. doi: 10.1371/journal.ppat.1000467 19503824

32. de Castro MG, de Nogueira FB, Nogueira RM, Lourenco-de-Oliveira R, dos Santos FB (2013) Genetic variation in the 3' untranslated region of dengue virus serotype 3 strains isolated from mosquitoes and humans in Brazil. Virol J 10: 3. doi: 10.1186/1743-422X-10-3 23282086

33. Chen R, Wang E, Tsetsarkin KA, Weaver SC (2013) Chikungunya virus 3' untranslated region: adaptation to mosquitoes and a population bottleneck as major evolutionary forces. PLoS Pathog 9: e1003591. doi: 10.1371/journal.ppat.1003591 24009512

34. Gubler D. KG, and Markoff L. (2007) Flaviviruses. In: Fields Virology. Philadelphia: Lippincott-Raven.

35. Ramirez C, Gregori J, Buti M, Tabernero D, Camos S, et al. (2013) A comparative study of ultra-deep pyrosequencing and cloning to quantitatively analyze the viral quasispecies using hepatitis B virus infection as a model. Antiviral Res 98: 273–283. doi: 10.1016/j.antiviral.2013.03.007 23523552

36. Casari G, Sander C, Valencia A (1995) A method to predict functional residues in proteins. Nat Struct Biol 2: 171–178. doi: 10.1038/nsb0295-171 7749921

37. Wilkinson KA, Merino EJ, Weeks KM (2006) Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE): quantitative RNA structure analysis at single nucleotide resolution. Nat Protoc 1: 1610–1616. doi: 10.1038/nprot.2006.249 17406453

38. Weeks KM, Mauger DM (2011) Exploring RNA structural codes with SHAPE chemistry. Acc Chem Res 44: 1280–1291. doi: 10.1021/ar200051h 21615079

39. Gruber AR, Findeiss S, Washietl S, Hofacker IL, Stadler PF (2010) RNAz 2.0: improved noncoding RNA detection. Pac Symp Biocomput: 69–79. 19908359

40. Lorenz R, Bernhart SH, Honer Zu Siederdissen C, Tafer H, Flamm C, et al. (2011) ViennaRNA Package 2.0. Algorithms Mol Biol 6: 26. doi: 10.1186/1748-7188-6-26 22115189

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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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PLOS Pathogens


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