Skip to main content

Advertisement

Log in

Ebolavirus evolves in human to minimize the detection by immune cells by accumulating adaptive mutations

  • Original Article
  • Published:
VirusDisease Aims and scope Submit manuscript

Abstract

The current outbreak of Zaire ebolavirus (EBOV) lasted longer than the previous outbreaks and there is as yet no proven treatment or vaccine available. Understanding host immune pressure and associated EBOV immune evasion that drive the evolution of EBOV is vital for diagnosis as well as designing a highly effective vaccine. The aim of this study was to deduce adaptive selection pressure acting on each amino acid sites of EBOV responsible for the recent 2014 outbreak. Multiple statistical methods employed in the study include SLAC, FEL, REL, IFEL, FUBAR and MEME. Results show that a total of 11 amino acid sites from sGP and ssGP, and 14 sites from NP, VP40, VP24 and L proteins were inferred as positively and negatively selected, respectively. Overall, the function of 11 out of 25 amino acid sites under selection pressure exactly found to be involved in T cell and B-cell epitopes. We identified that the EBOV had evolved through purifying selection pressure, which is a predictor that is known to aid the virus to adapt better to the human host and subsequently reduce the efficiency of existing immunity. Furthermore, computational RNA structure prediction showed that the three synonymous nucleotide mutations in NP gene altered the RNA secondary structure and optimal base-pairing energy, implicating a possible effect on genome replication. Here, we have provided evidence that the EBOV strains involved in the recent 2014 outbreak have evolved to minimize the detection by T and B cells by accumulating adaptive mutations to increase the survival fitness.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Arunachalam R. Adaptive evolution of a novel avian-origin influenza A/H7N9 virus. Genomics. 2014;104:545–53.

    Article  CAS  PubMed  Google Scholar 

  2. Arunachalam R. Detection of site-specific positive Darwinian selection on pandemic influenza A/H1N1 virus genome: integrative approaches. Genetica. 2013;141:143–55.

    Article  CAS  PubMed  Google Scholar 

  3. Becquart P, Mahlakoiv T, Nkoghe D, Leroy EM. Identification of continuous human B-cell epitopes in the VP35, VP40, nucleoprotein and glycoprotein of ebola virus. PLoS ONE. 2014;9:e96360.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Chu D, Ren S, Hu S, Wang WG, Subramanian A, Contreras D, Kanagavel V, Chung E, Ko J, Appadorai RSAJ, Sinha S, Jalali Z, Hardy DW, French SW, Arumugaswami V. Systematic analysis of enhancer and critical cis-acting RNA elements in the protein-encoding region of the hepatitis C virus genome. J Virol. 2013;87:5678–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Comas I, Chakravartti J, Small PM, Galagan J, Niemann S, Kremer K, Ernst JD, Gagneux S. Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved. Nat Genet. 2010;42:498–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cusick MF, Wang S, Eckels DD. In vitro responses to avian influenza H5 by human CD4 T cells. J Immunol. 2009;183:6432–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. de La Vega M-A, Wong G, Kobinger GP, Qiu X. The multiple roles of sGP in Ebola pathogenesis. Viral Immunol. 2014;28:1–7.

    Google Scholar 

  8. Delport W, Poon A-FY, Frost SDW, Pond SLK. Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology. Bioinformatics. 2010;2010(26):2455–7.

    Article  Google Scholar 

  9. Farci P, Shimoda A, Coiana A, Diaz G, Peddis G, Melpolder JC, Strazzera A, Chien DY, Munoz SJ, Balestrieri A, Purcell RH, Alter HJ. The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Science. 2000;288:339–44.

    Article  CAS  PubMed  Google Scholar 

  10. Furuse Y, Shimabukuro K, Odagiri T, Sawayama R, Okada T, Khandaker I, Suzuki A, Oshitani H. Comparison of selection pressures on the HA gene of pandemic (2009) and seasonal human and swine influenza A H1 subtype viruses. Virology. 2010;405:314–21.

    Article  CAS  PubMed  Google Scholar 

  11. Geisbert TW, Jahrling PB. Differentiation of filoviruses by electron microscopy. Virus Res. 1995;39:129–50.

    Article  CAS  PubMed  Google Scholar 

  12. Harty RN, Brown ME, Wang G, Huibregtse J, Hayes FP. A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: implications for filovirus budding. Proc Natl Acad Sci U S A. 2000;97:13871–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14:36–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Johnson RF, Bell P, Harty RN. Effect of Ebola virus proteins GP, NP and VP35 on VP40 VLP morphology. Virol J. 2006;3:31.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Jun SR, Leuze MR, Nookaew I, Uberbacher EC, Land M, Zhang Q, Wanchai V, Chai J, Nielsen M, Trolle T, Lund O, Buzard GS, Pedersen TD, Wassenaar TM, Ussery DW. Ebolavirus comparative genomics. FEMS Microbiol Rev. 2015;39:764–78.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kawashima Y, Pfafferott K, Frater J, Matthews P, Payne R, Addo M, Gatanaga H, Fujiwara M, Hachiya A, Koizumi H, Kuse N, Oka S, Duda A, Prendergast A, Crawford H, Leslie A, Brumme Z, Brumme C, Allen T, Brander C, Kaslow R, Tang J, Hunter E, Allen S, Mulenga J, Branch S, Roach T, John M, Mallal S, Ogwu A, Shapiro R, Prado JG, Fidler S, Weber J, Pybus OG, Klenerman P, Ndung’u T, Phillips R, Heckerman D, Harrigan PR, Walker BD, Takiguchi M, Goulder P. Adaptation of HIV-1 to human leukocyte antigen class I. Nature. 2009;458:641–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kindzelskii AL, Yang Z, Nabel GJ, Todd RF, Petty HR. Ebola virus secretory glycoprotein (sGP) diminishes Fc gamma RIIIB-to-CR3 proximity on neutrophils. J Immunol. 2000;164:953–8.

    Article  CAS  PubMed  Google Scholar 

  18. Misasi J, Sullivan NJ. Camouflage and misdirection: the full-on assault of Ebola virus disease. Cell. 2014;159:477–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mohamadzadeh M, Chen L, Schmaljohn AL. How Ebola and Marburg viruses battle the immune system. Nat Rev Immunol. 2007;7:556–67.

    Article  CAS  PubMed  Google Scholar 

  20. Mohan GS, Li W, Ye L, Compans RW, Yang C. Antigenic subversion: a novel mechanism of host immune evasion by Ebola virus. PLoS Pathog. 2012;8:e1003065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Muhlberger E, Weik M, Volchkov VE, Klenk HD, Becker S. Comparison of the transcription and replication strategies of Marburg virus and Ebola virus by using artiÆcial replication systems. J Virol. 1999;73:2333–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Murrell B, Moola S, Mabona A, Weighill T, Sheward D, Pond SLK, Scheffler K. FUBAR: a fast, unconstrained Bayesian approximation for inferring selection. Mol Biol Evol. 2013;30:1196–205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005;5:375–86.

    Article  CAS  PubMed  Google Scholar 

  24. Pond SLK, Frost SDW, Grossman Z, Gravenor MB, Richman DD, Brown AJ. Adaptation to different human populations by HIV-1 revealed by codon-based analyses. PLoS Comput Biol. 2006;2:e62.

    Article  PubMed  Google Scholar 

  25. Pond SLK, Frost SDW. Not so different after all: a comparison of methods for detecting amino acid sited under selection. Mol Biol Evol. 2005;22:1208–22.

    Article  CAS  Google Scholar 

  26. Pond SLK, Murrell B, Fourment M, Frost SDW, Delport W, Scheffler K. A random effects branch-site model for detecting episodic diversifying selection. Mol Biol Evol. 2011;28:3033–43.

    Article  Google Scholar 

  27. Reid SP, Leung LW, Hartman AL, Martinez O, Shaw ML, Carbonnelle C, Volchkov VE, Nichol ST, Basler CF. Ebola virus VP24 binds karyopherin alpha1 and blocks STAT1 nuclear accumulation. J Virol. 2006;80:5156–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Ross AGP, Olveda RM, Yuesheng L. Are we ready for a global pandemic of Ebola virus? Int J Infect Dis. 2014;28:217–8.

    Article  PubMed  Google Scholar 

  29. Suzuki Y. Natural selection on the influenza virus genome. Mol Biol Evol. 2006;23:1902–11.

    Article  CAS  PubMed  Google Scholar 

  30. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol. 2013;30:2725–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Vita R, Zarebski L, Greenbaum JA, Emami H, Hoof I, Salimi N, Damle R, Sette A, Peters B. The immune epitope database 2. Nucleic Acids Res. 2010;38:D854–62.

    Article  CAS  PubMed  Google Scholar 

  32. Yang Z, Delgado R, Xu L, Todd RF, Nabel EG, Sanchez A, Nabel GJ. Distinct cellular interactions of secreted and transmembrane Ebola virus glycoproteins. Science. 1998;279:1034–7.

    Article  CAS  PubMed  Google Scholar 

  33. Zuker M. mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 2003;31:3406–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We are grateful to authors and researchers who have made available of all 2014 EBOV genomic sequences in the public database. No funders had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Deisy Contreras of Cedars-Sinai Medical Center, Los Angeles for editing this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Arunachalam Ramaiah.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 52 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ramaiah, A., Arumugaswami, V. Ebolavirus evolves in human to minimize the detection by immune cells by accumulating adaptive mutations. VirusDis. 27, 136–144 (2016). https://doi.org/10.1007/s13337-016-0305-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13337-016-0305-0

Keywords

Navigation