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Volume 21, Number 7—July 2015
Research

Monitoring of Ebola Virus Makona Evolution through Establishment of Advanced Genomic Capability in Liberia

Jeffrey R. Kugelman1, Michael R. Wiley1, Suzanne Mate1, Jason T. Ladner1, Brett Beitzel, Lawrence Fakoli, Fahn Taweh, Karla Prieto, Joseph W. Diclaro, Timothy Minogue, Randal J. Schoepp, Kurt E. Schaecher, James Pettitt, Stacey Bateman, Joseph Fair, Jens H. Kuhn, Lisa Hensley, Daniel J. Park, Pardis C. Sabeti, Mariano Sanchez-Lockhart, Fatorma K. Bolay, Gustavo PalaciosComments to Author , on behalf of US Army Medical Research Institute of Infectious DiseasesNational Institutes of HealthIntegrated Research Facility–Frederick Ebola Response Team 2014–2015
Author affiliations: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, USA (J.R. Kugelman, M.R. Wiley, S. Mate, J.T. Ladner, B. Beitzel, K. Prieto, T. Minogue, R.J. Schoepp, K.E. Schaecher, S. Bateman, M. Sanchez-Lockhart, G. Palacios); Liberian Institute for Biomedical Research, Charlesville, Liberia (L. Fakoli, F. Taweh, F.K. Bolay); Naval Medical Research Unit 3, Cairo, Egypt (J.W. Diclaro); Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick (J. Pettitt, J.H. Kuhn, L. Hensley); Foundation Merieux, Washington, DC, USA (J. Fair); Broad Institute, Cambridge, Massachusetts, USA (D.J. Park, P.C. Sabeti); Center for Systems Biology, Harvard University, Cambridge (P.C. Sabeti)

Main Article

Figure 1

A) Median-joining haplotype network constructed from a full-genome alignment of 122 clinical Ebola virus Makona (EBOV/Mak) isolates (list of isolates in Technical Appendix 3). Each colored vertex represents a sampled viral haplotype, with the numbered vertices representing the centers of the 3 clusters described in (12). All sampled isolates from Liberia originated from cluster 2. The size of each vertex is relative to the number of sampled isolates, and the colors indicate country of origin. Ha

Figure 1. A) Median-joining haplotype network constructed from a full-genome alignment of 122 clinical Ebola virus Makona (EBOV/Mak) isolates (list of isolates in Technical Appendix 3). Each colored vertex represents a sampled viral haplotype, with the numbered vertices representing the centers of the 3 clusters described in (12). All sampled isolates from Liberia originated from cluster 2. The size of each vertex is relative to the number of sampled isolates, and the colors indicate country of origin. Hatch marks indicate the number of mutations along each edge. Because of missing data, 2,764 sites (14.6% of total genome) were excluded from the analysis, including 26 sites with variability among isolates (16.7% of all variable sites). B) Root-to-tip distance correlates well with test date and estimates a rate of evolution equal to 9.17 × 10−4 substitutions/site/year. This analysis comprises 110 clinical EBOV/Mak isolates collected during March 17, 2014–January 20, 2015 (Technical Appendix 3, isolates with dates).

Main Article

References
  1. Baize  S, Pannetier  D, Oestereich  L, Rieger  T, Koivogui  L, Magassouba  N, Emergence of Zaire Ebola virus disease in Guinea—preliminary report. N Engl J Med. 2014;371:1418–25 . DOIPubMedGoogle Scholar
  2. Hawkes  N. Ebola outbreak is a public health emergency of international concern, WHO warns. BMJ. 2014;349:g5089. DOIPubMedGoogle Scholar
  3. Yozwiak  NL, Schaffner  SF, Sabeti  PC. Data sharing: make outbreak research open access. Nature. 2015;518:477–9. DOIPubMedGoogle Scholar
  4. World Health Organization. Ebola situation report—11 March 2015 [cited 2015 Mar 30]. http://apps.who.int/ebola/current-situation/ebola-situation-report-11-march-2015
  5. Chan  M. WHO report by the Director-General to the special session of the Executive Board on Ebola [cited 2015 Mar 30]. http://www.who.int/dg/speeches/2015/executive-board-ebola/en/
  6. Kugelman  JR, Sanchez-Lockhart  M, Andersen  KG, Gire  S, Park  DJ, Sealfon  R, Evaluation of the potential impact of Ebola virus genomic drift on the efficacy of sequence-based candidate therapeutics. MBio. 2015;6:e02227–14. DOIPubMedGoogle Scholar
  7. Shuchman  M. WHO enters new terrain in Ebola research. CMAJ. 2014;186:E527–8. DOIPubMedGoogle Scholar
  8. Sayburn  A. WHO gives go ahead for experimental treatments to be used in Ebola outbreak. BMJ. 2014;349:g5161. DOIPubMedGoogle Scholar
  9. Trombley  AR, Wachter  L, Garrison  J, Buckley-Beason  VA, Jahrling  J, Hensley  LE, Comprehensive panel of real-time TaqMan polymerase chain reaction assays for detection and absolute quantification of filoviruses, arenaviruses, and New World hantaviruses. Am J Trop Med Hyg. 2010;82:954–60. DOIPubMedGoogle Scholar
  10. Kuhn  JH, Andersen  KG, Baize  S, Bao  Y, Bavari  S, Berthet  N, Nomenclature- and database-compatible names for the two Ebola virus variants that emerged in Guinea and the Democratic Republic of the Congo in 2014. Viruses. 2014;6:4760–99. DOIPubMedGoogle Scholar
  11. Djikeng  A, Halpin  R, Kuzmickas  R, Depasse  J, Feldblyum  J, Sengamalay  N, Viral genome sequencing by random priming methods. BMC Genomics. 2008;9:5. DOIPubMedGoogle Scholar
  12. Gire  SK, Goba  A, Andersen  KG, Sealfon  RS, Park  DJ, Kanneh  L, Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science. 2014;345:1369–72. DOIPubMedGoogle Scholar
  13. Martin  M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnetjournal. 2011;17:10–2.
  14. Schmieder  R, Edwards  R. Quality control and preprocessing of metagenomic datasets. Bioinformatics. 2011;27:863–4. DOIPubMedGoogle Scholar
  15. Li  H, Handsaker  B, Wysoker  A, Fennell  T, Ruan  J, Homer  N, The sequence alignment/map format and SAMtools. Bioinformatics. 2009;25:2078–9. DOIPubMedGoogle Scholar
  16. Cingolani  P, Platts  A. Wang le L, Coon M, Nguyen T, Wang L, et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly (Austin). 2012;6:80–92.
  17. Drummond  AJ, Suchard  MA, Xie  D, Rambaut  A. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol Biol Evol. 2012;29:1969–73. DOIPubMedGoogle Scholar
  18. Guindon  S, Dufayard  JF, Lefort  V, Anisimova  M, Hordijk  W, Gascuel  O. New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol. 2010;59:307–21. DOIPubMedGoogle Scholar
  19. Ladner  JT, Beitzel  B, Chain  PS, Davenport  MG, Donaldson  EF, Frieman  M, Standards for sequencing viral genomes in the era of high-throughput sequencing. MBio. 2014;5:e01360–14. DOIPubMedGoogle Scholar
  20. Geisbert  TW, Lee  AC, Robbins  M, Geisbert  JB, Honko  AN, Sood  V, Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study. Lancet. 2010;375:1896–905. DOIPubMedGoogle Scholar
  21. Warren  TK, Warfield  KL, Wells  J, Swenson  DL, Donner  KS, Van Tongeren  SA, Advanced antisense therapies for postexposure protection against lethal filovirus infections. Nat Med. 2010;16:991–4. DOIPubMedGoogle Scholar
  22. Qiu  X, Audet  J, Wong  G, Fernando  L, Bello  A, Pillet  S, Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb. Sci Rep. 2013;3:3365.
  23. Pettitt  J, Zeitlin  L, Kim  DH, Working  C, Johnson  JC, Bohorov  O, Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB-003 monoclonal antibody cocktail. Sci Transl Med. 2013;5:199ra113. PMID: 23966302
  24. Qiu  X, Wong  G, Audet  J, Bello  A, Fernando  L, Alimonti  JB, Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature. 2014;514:47–53 .PubMedGoogle Scholar
  25. Olinger  GG Jr, Pettitt  J, Kim  D, Working  C, Bohorov  O, Bratcher  B, Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques. Proc Natl Acad Sci U S A. 2012;109:18030–5. DOIPubMedGoogle Scholar
  26. Dye  JM, Herbert  AS, Kuehne  AI, Barth  JF, Muhammad  MA, Zak  SE, Postexposure antibody prophylaxis protects nonhuman primates from filovirus disease. Proc Natl Acad Sci U S A. 2012;109:5034–9. DOIPubMedGoogle Scholar
  27. Heald  AE, Iversen  PL, Saoud  JB, Sazani  P, Charleston  JS, Axtelle  T, Safety and pharmacokinetic profiles of phosphorodiamidate morpholino oligomers with activity against Ebola virus and Marburg virus: results of two single-ascending-dose studies. Antimicrob Agents Chemother. 2014;58:6639–47. DOIPubMedGoogle Scholar
  28. Kuhn  JH, Bao  Y, Bavari  S, Becker  S, Bradfute  S, Brister  JR, Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae. Arch Virol. 2013;158:301–11. DOIPubMedGoogle Scholar
  29. Rezler  JP. Tekmira provides periodic update on TKM-Ebola program [cited 2015 Mar 30]. http://investor.tekmirapharm.com/releasedetail.cfm?ReleaseID=877397
  30. Wilson  JA, Hevey  M, Bakken  R, Guest  S, Bray  M, Schmaljohn  AL, Epitopes involved in antibody-mediated protection from Ebola virus. Science. 2000;287:1664–6. DOIPubMedGoogle Scholar
  31. Qiu  X, Alimonti  JB, Melito  PL, Fernando  L, Stroher  U, Jones  SM. Characterization of Zaire ebolavirus glycoprotein-specific monoclonal antibodies. Clin Immunol. 2011;141:218–27 . DOIPubMedGoogle Scholar
  32. Towner  JS, Paragas  J, Dover  JE, Gupta  M, Goldsmith  CS, Huggins  JW, Generation of eGFP expressing recombinant Zaire ebolavirus for analysis of early pathogenesis events and high-throughput antiviral drug screening. Virology. 2005;332:20–7. DOIPubMedGoogle Scholar
  33. Swenson  DL, Warfield  KL, Warren  TK, Lovejoy  C, Hassinger  JN, Ruthel  G, Chemical modifications of antisense morpholino oligomers enhance their efficacy against Ebola virus infection. Antimicrob Agents Chemother. 2009;53:2089–99. DOIPubMedGoogle Scholar
  34. Geisbert  TW, Hensley  LE, Kagan  E, Yu  EZ, Geisbert  JB, Daddario-DiCaprio  K, Postexposure protection of guinea pigs against a lethal Ebola virus challenge is conferred by RNA interference. J Infect Dis. 2006;193:1650–7. DOIPubMedGoogle Scholar
  35. Theriault  S, Groseth  A, Neumann  G, Kawaoka  Y, Feldmann  H. Rescue of Ebola virus from cDNA using heterologous support proteins. Virus Res. 2004;106:43–50. DOIPubMedGoogle Scholar
  36. Martínez  MJ, Biedenkopf  N, Volchkova  V, Hartlieb  B, Alazard-Dany  N, Reynard  O, Role of Ebola virus VP30 in transcription reinitiation. J Virol. 2008;82:12569–73. DOIPubMedGoogle Scholar
  37. Biedenkopf  N, Hartlieb  B, Hoenen  T, Becker  S. Phosphorylation of Ebola virus VP30 influences the composition of the viral nucleocapsid complex: impact on viral transcription and replication. J Biol Chem. 2013;288:11165–74. DOIPubMedGoogle Scholar
  38. Carroll  SA, Towner  JS, Sealy  TK, McMullan  LK, Khristova  ML, Burt  FJ, Molecular evolution of viruses of the family Filoviridae based on 97 whole-genome sequences. J Virol. 2013;87:2608–16. DOIPubMedGoogle Scholar
  39. World Health Organization. Mali: details of the additional cases of Ebola virus disease [cited 2015 Mar 30]. http://www.who.int/mediacentre/news/ebola/20-november-2014-mali/en/

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1These authors contributed equally to this article.

Page created: June 12, 2015
Page updated: June 12, 2015
Page reviewed: June 12, 2015
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
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