Multiscale analysis for patterns of Zika virus genotype emergence, spread, and consequence


Autoři: Monica K. Borucki aff001;  Nicole M. Collette aff001;  Lark L. Coffey aff002;  Koen K. A. Van Rompay aff002;  Mona H. Hwang aff001;  James B. Thissen aff001;  Jonathan E. Allen aff004;  Adam T. Zemla aff004
Působiště autorů: Physical Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California, United States of America aff001;  Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America aff002;  California National Primate Research Center, University of California Davis, Davis, California, United States of America aff003;  Computations Directorate, Lawrence Livermore National Laboratory, Livermore, California, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225699

Souhrn

The question of how Zika virus (ZIKV) changed from a seemingly mild virus to a human pathogen capable of microcephaly and sexual transmission remains unanswered. The unexpected emergence of ZIKV’s pathogenicity and capacity for sexual transmission may be due to genetic changes, and future changes in phenotype may continue to occur as the virus expands its geographic range. Alternatively, the sheer size of the 2015–16 epidemic may have brought attention to a pre-existing virulent ZIKV phenotype in a highly susceptible population. Thus, it is important to identify patterns of genetic change that may yield a better understanding of ZIKV emergence and evolution. However, because ZIKV has an RNA genome and a polymerase incapable of proofreading, it undergoes rapid mutation which makes it difficult to identify combinations of mutations associated with viral emergence. As next generation sequencing technology has allowed whole genome consensus and variant sequence data to be generated for numerous virus samples, the task of analyzing these genomes for patterns of mutation has become more complex. However, understanding which combinations of mutations spread widely and become established in new geographic regions versus those that disappear relatively quickly is essential for defining the trajectory of an ongoing epidemic. In this study, multiscale analysis of the wealth of genomic data generated over the course of the epidemic combined with in vivo laboratory data allowed trends in mutations and outbreak trajectory to be assessed. Mutations were detected throughout the genome via deep sequencing, and many variants appeared in multiple samples and in some cases become consensus. Similarly, amino acids that were previously consensus in pre-outbreak samples were detected as low frequency variants in epidemic strains. Protein structural models indicate that most of the mutations associated with the epidemic transmission occur on the exposed surface of viral proteins. At the macroscale level, consensus data was organized into large and interactive databases to allow the spread of individual mutations and combinations of mutations to be visualized and assessed for temporal and geographical patterns. Thus, the use of multiscale modeling for identifying mutations or combinations of mutations that impact epidemic transmission and phenotypic impact can aid the formation of hypotheses which can then be tested using reverse genetics.

Klíčová slova:

Macaque – Microbial mutation – Mutation databases – Mutation detection – Protein structure – Sequence databases – Structural genomics – Zika virus


Zdroje

1. Dick GWA (1952) Zika virus (II). Pathogenicity and physical properties. Transactions of The Royal Society of Tropical Medicine and Hygiene 46: 521–534. doi: 10.1016/0035-9203(52)90043-6 12995441

2. Li C, Xu D, Ye Q, Hong S, Jiang Y, Liu X, et al. (2016) Zika Virus Disrupts Neural Progenitor Development and Leads to Microcephaly in Mice. Cell Stem Cell.

3. Miner Jonathan J, Cao B, Govero J, Smith Amber M, Fernandez E, Cabrera Omar H, et al. (2016) Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise. Cell.

4. Mlakar J, Korva M, Tul N, Popović M, Poljšak-Prijatelj M, Mraz J, et al. (2016) Zika Virus Associated with Microcephaly. New England Journal of Medicine 0: null.

5. Tang H, Hammack C, Ogden Sarah C, Wen Z, Qian X, Li Y, et al. (2016) Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth. Cell Stem Cell.

6. Wang L, Valderramos Stephanie G, Wu A, Ouyang S, Li C, Brasil P, et al. (2016) From Mosquitos to Humans: Genetic Evolution of Zika Virus. Cell Host & Microbe.

7. Allard A, Althouse BM, Hébert-Dufresne L, Scarpino SV (2017) The risk of sustained sexual transmission of Zika is underestimated. PLOS Pathogens 13: e1006633. doi: 10.1371/journal.ppat.1006633 28934370

8. Carroll T, Lo M, Lanteri M, Dutra J, Zarbock K, Silveira P, et al. (2017) Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques. PLOS Pathogens 13: e1006537. doi: 10.1371/journal.ppat.1006537 28746373

9. García-Bujalance S, Gutiérrez-Arroyo A, De la Calle F, Díaz-Menéndez M, Arribas JR, García-Rodríguez J, et al. (2017) Persistence and infectivity of Zika virus in semen after returning from endemic areas: Report of 5 cases. Journal of Clinical Virology 96: 110–115. doi: 10.1016/j.jcv.2017.10.006 29053990

10. Mansuy JM, Dutertre M, Mengelle C, Fourcade C, Marchou B, Delobel P, et al. (2016) Zika virus: high infectious viral load in semen, a new sexually transmitted pathogen. Lancet Infect Dis 16: 00138–00139.

11. Moreira J, Peixoto TM, Machado de Siqueira A, Lamas CC (2016) Sexually acquired Zika virus: a systematic review. Clinical Microbiology and Infection.

12. Musso D, Roche C, Robin E, Nhan T, Teissier A, Cao-Lormeau VM (2015) Potential sexual transmission of Zika virus. Emerg Infect Dis 21: 359–361. doi: 10.3201/eid2102.141363 25625872

13. Kuno G, Chang GJ, Tsuchiya KR, Karabatsos N, Cropp CB (1998) Phylogeny of the genus Flavivirus. Journal of virology 72: 73–83. 9420202

14. Dick GW, Kitchen SF, Haddow AJ (1952) Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg 46: 509–520. doi: 10.1016/0035-9203(52)90042-4 12995440

15. Haddow AJ, Williams MC, Woodall JP, Simpson DI, Goma LK (1964) TWELVE ISOLATIONS OF ZIKA VIRUS FROM AEDES (STEGOMYIA) AFRICANUS (THEOBALD) TAKEN IN AND ABOVE A UGANDA FOREST. Bull World Health Organ 31: 57–69. 14230895

16. Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, et al. (2008) Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 14: 1232–1239. doi: 10.3201/eid1408.080287 18680646

17. Marchette NJ, Garcia R, Rudnick A (1969) Isolation of Zika Virus from Aedes Aegypti Mosquitoes in Malaysia*. 18: 411–415.

18. World Health Organization: The WHO child growth standards. [cited 2013 April 15]. http://www.who.int/childgrowth/en.

19. Kuno G, Chang G-JJ (2005) Biological transmission of arboviruses: reexamination of and new insights into components, mechanisms, and unique traits as well as their evolutionary trends. Clinical microbiology reviews 18: 608–637. doi: 10.1128/CMR.18.4.608-637.2005 16223950

20. Goo L, DeMaso CR, Pelc RS, Ledgerwood JE, Graham BS, Kuhn RJ, et al. (2018) The Zika virus envelope protein glycan loop regulates virion antigenicity. Virology 515: 191–202. doi: 10.1016/j.virol.2017.12.032 29304471

21. Kumar A, Hou S, Airo AM, Limonta D, Mancinelli V, Branton W, et al. (2016) Zika virus inhibits type-I interferon production and downstream signaling. EMBO reports.

22. Xia H, Luo H, Shan C, Muruato AE, Nunes BTD, Medeiros DBA, et al. (2018) An evolutionary NS1 mutation enhances Zika virus evasion of host interferon induction. Nature Communications 9: 414. doi: 10.1038/s41467-017-02816-2 29379028

23. Grant A, Ponia SS, Tripathi S, Balasubramaniam V, Miorin L, Sourisseau M, et al. (2016) Zika Virus Targets Human STAT2 to Inhibit Type I Interferon Signaling. Cell Host Microbe 19: 882–890. doi: 10.1016/j.chom.2016.05.009 27212660

24. Wu Y, Liu Q, Zhou J, Xie W, Chen C, Wang Z, et al. (2017) Zika virus evades interferon-mediated antiviral response through the co-operation of multiple nonstructural proteins in vitro. Cell Discov 3.

25. Domingo E, Sheldon J, Perales C (2012) Viral quasispecies evolution. Microbiol Mol Biol Rev 76.

26. Pesko KN, Ebel GD (2012) West Nile virus population genetics and evolution. Infection, Genetics and Evolution 12: 181–190. doi: 10.1016/j.meegid.2011.11.014 22226703

27. Ciota AT, Ehrbar DJ, Van Slyke GA, Willsey GG, Kramer LD (2012) Cooperative interactions in the West Nile virus mutant swarm. BMC Evolutionary Biology 12: 1–9.

28. Stapleford Kenneth A, Coffey Lark L, Lay S, Bordería Antonio V, Duong V, Isakov O, et al. (2014) Emergence and Transmission of Arbovirus Evolutionary Intermediates with Epidemic Potential. Cell Host & Microbe 15: 706–716.

29. Faria NR, Azevedo RdSdS, Kraemer MUG, Souza R, Cunha MS, Hill SC, et al. (2016) Zika virus in the Americas: Early epidemiological and genetic findings. Science.

30. Zhu Z, Chan JF-W, Tee K-M, Choi GK-Y, Lau SK-P, Woo PC-Y, et al. (2016) Comparative genomic analysis of pre-epidemic and epidemic Zika virus strains for virological factors potentially associated with the rapidly expanding epidemic. Emerg Microbes Infect 5: e22. doi: 10.1038/emi.2016.48 26980239

31. Hadfield J, Megill C, Bell SM, Huddleston J, Potter B, Callender C, et al. (2018) Nextstrain: real-time tracking of pathogen evolution. Bioinformatics 34: 4121–4123. doi: 10.1093/bioinformatics/bty407 29790939

32. Faria NR, Quick J, Claro IM, Thézé J, de Jesus JG, Giovanetti M, et al. (2017) Establishment and cryptic transmission of Zika virus in Brazil and the Americas. Nature 546: 406. doi: 10.1038/nature22401 28538727

33. Lednicky J, Beau De Rochars VM, El Badry M, Loeb J, Telisma T, Chavannes S, et al. (2016) Zika Virus Outbreak in Haiti in 2014: Molecular and Clinical Data. PLoS Neglected Tropical Diseases 10: e0004687. doi: 10.1371/journal.pntd.0004687 27111294

34. Metsky HC, Matranga CB, Wohl S, Schaffner SF, Freije CA, Winnicki SM, et al. (2017) Zika virus evolution and spread in the Americas. Nature 546: 411. doi: 10.1038/nature22402 28538734

35. Borucki MK, Chen-Harris H, Lao V, Vanier G, Wadford DA, Messenger S, et al. (2013) Ultra-Deep Sequencing of Intra-host Rabies Virus Populations during Cross-species Transmission. PLoS Negl Trop Dis 7: e2555. doi: 10.1371/journal.pntd.0002555 24278493

36. Lazear Helen M, Govero J, Smith Amber M, Platt Derek J, Fernandez E, Miner Jonathan J, et al. (2016) A Mouse Model of Zika Virus Pathogenesis. Cell Host & Microbe.

37. Ciota AT, Ehrbar DJ, Van Slyke GA, Payne AF, Willsey GG, Viscio RE, et al. (2012) Quantification of intrahost bottlenecks of West Nile virus in Culex pipiens mosquitoes using an artificial mutant swarm. Infection, Genetics and Evolution 12: 557–564. doi: 10.1016/j.meegid.2012.01.022 22326536

38. Jerzak GVS, Brown I, Shi P-Y, Kramer LD, Ebel GD (2008) Genetic diversity and purifying selection in West Nile virus populations are maintained during host switching. Virology 374: 256–260. doi: 10.1016/j.virol.2008.02.032 18395240

39. Coffey LL, Keesler RI, Pesavento PA, Woolard K, Singapuri A, Watanabe J, et al. (2018) Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease. Nature Communications 9: 2414. doi: 10.1038/s41467-018-04777-6 29925843

40. Chen-Harris H, Borucki MK, Torres C, Slezak TR, Allen JE (2013) Ultra-deep mutant spectrum profiling: improving sequencing accuracy using overlapping read pairs. BMC Genomics 14: 96–96. doi: 10.1186/1471-2164-14-96 23402258

41. Lanciotti RS, Lambert AJ, Holodniy M, Saavedra S, Signor LdCC (2016) Phylogeny of Zika Virus in Western Hemisphere, 2015. Emerging Infectious Diseases 22: 933–935. doi: 10.3201/eid2205.160065 27088323

42. Duggal NK, McDonald EM, Weger-Lucarelli J, Hawks SA, Ritter JM, Romo H, et al. (2019) Mutations present in a low-passage Zika virus isolate result in attenuated pathogenesis in mice. Virology 530: 19–26. doi: 10.1016/j.virol.2019.02.004 30763872

43. Ciota AT, Lovelace AO, Ngo KA, Le AN, Maffei JG, Franke MA, et al. (2007) Cell-specific adaptation of two flaviviruses following serial passage in mosquito cell culture. Virology 357: 165–174. doi: 10.1016/j.virol.2006.08.005 16963095

44. Ciota AT, Ngo KA, Lovelace AO, Payne AF, Zhou Y, Shi P-Y, et al. (2007) Role of the mutant spectrum in adaptation and replication of West Nile virus. The Journal of general virology 88: 865–874. doi: 10.1099/vir.0.82606-0 17325359

45. Tsetsarkin KA, Kenney H, Chen R, Liu G, Manukyan H, Whitehead SS, et al. (2016) A Full-Length Infectious cDNA Clone of Zika Virus from the 2015 Epidemic in Brazil as a Genetic Platform for Studies of Virus-Host Interactions and Vaccine Development. mBio 7.

46. van Boheemen S, Tas A, Anvar SY, van Grootveld R, Albulescu IC, Bauer MP, et al. (2017) Quasispecies composition and evolution of a typical Zika virus clinical isolate from Suriname. Scientific Reports 7: 2368. doi: 10.1038/s41598-017-02652-w 28539654

47. Kyte J, Doolittle RF (1982) A simple method for displaying the hydropathic character of a protein. J Mol Biol 157: 105–132. doi: 10.1016/0022-2836(82)90515-0 7108955

48. Zemla A (2003) LGA: A method for finding 3D similarities in protein structures. Nucleic Acids Res 31: 3370–3374. doi: 10.1093/nar/gkg571 12824330

49. Zemla A, Kostova T, Gorchakov R, Volkova E, Beasley DWC, Cardosa J, et al. (2014) GeneSV–an Approach to Help Characterize Possible Variations in Genomic and Protein Sequences. Bioinformatics and Biology Insights 8: 1–16. doi: 10.4137/BBI.S13076 24453480

50. Zemla A, Zhou CE, Slezak T, Kuczmarski T, Rama D, Torres C, et al. (2005) AS2TS system for protein structure modeling and analysis. Nucleic Acids Res 33.

51. Tay MYF, Saw WG, Zhao Y, Chan KWK, Singh D, Chong Y, et al. (2015) The C-terminal 50 Amino Acid Residues of Dengue NS3 Protein Are Important for NS3-NS5 Interaction and Viral Replication. Journal of Biological Chemistry 290: 2379–2394. doi: 10.1074/jbc.M114.607341 25488659

52. Liu Y, Liu J, Du S, Shan C, Nie K, Zhang R, et al. (2017) Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes. Nature 545: 482–486. doi: 10.1038/nature22365 28514450

53. Domingo E, Holland JJ (1997) RNA virus mutations and fitness for survival. Annual Review of Microbiology 51: 151–178. doi: 10.1146/annurev.micro.51.1.151 9343347

54. Wang C, Mitsuya Y, Gharizadeh B, Ronaghi M, Shafer RW (2007) Characterization of mutation spectra with ultra-deep pyrosequencing: application to HIV-1 drug resistance. Genome Res 17: 1195–1201. doi: 10.1101/gr.6468307 17600086

55. Team RC (2013) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. pp. http://www.R-project.org/.

56. Sheehan KC, Lai KS, Dunn GP, Bruce AT, Diamond MS, Heutel JD, et al. (2006) Blocking monoclonal antibodies specific for mouse IFN-alpha/beta receptor subunit 1 (IFNAR-1) from mice immunized by in vivo hydrodynamic transfection. J Interferon Cytokine Res 26: 804–819. doi: 10.1089/jir.2006.26.804 17115899

57. Sheehan KCF, Lazear HM, Diamond MS, Schreiber RD (2015) Selective Blockade of Interferon-α and -β Reveals Their Non-Redundant Functions in a Mouse Model of West Nile Virus Infection. PLOS ONE 10: e0128636. doi: 10.1371/journal.pone.0128636 26010249

58. Kamala T (2007) Hock immunization: A humane alternative to mouse footpad injections. Journal of immunological methods 328: 204–214. doi: 10.1016/j.jim.2007.08.004 17804011

59. Dowall SD, Graham VA, Rayner E, Atkinson B, Hall G, Watson RJ, et al. (2016) A susceptible mouse model for Zika virus infection. bioRxiv.

60. Coffey LL, Pesavento PA, Keesler RI, Singapuri A, Watanabe J, Watanabe R, et al. (2017) Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques. PLoS One 12: e0171148. doi: 10.1371/journal.pone.0171148 28141843

61. Quick J, Grubaugh ND, Pullan ST, Claro IM, Smith AD, Gangavarapu K, et al. (2017) Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples. Nature Protocols 12: 1261. doi: 10.1038/nprot.2017.066 28538739

62. Gardner SN, Jaing CJ, Elsheikh MM, Pena J, Hysom DA, Borucki MK (2014) Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes. Advances in Bioinformatics 2014: 8.

63. Yang J, Yan R, Roy A, Xu D, Poisson J, Zhang Y (2015) The I-TASSER Suite: protein structure and function prediction. Nat Methods 12: 7–8. doi: 10.1038/nmeth.3213 25549265

64. Zemla AT, Lang DM, Kostova T, Andino R, Ecale Zhou CL (2011) StralSV: assessment of sequence variability within similar 3D structures and application to polio RNA-dependent RNA polymerase. BMC Bioinformatics 12: 226–226. doi: 10.1186/1471-2105-12-226 21635786


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2019 Číslo 12