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Home / Equine Research Bank / Retrovirology / Genetic Evolution during the development of an attenuated EI...
Retrovirology2016; 13; 9; doi: 10.1186/s12977-016-0240-6

Genetic Evolution during the development of an attenuated EIAV vaccine.

Abstract: The equine infectious anemia virus (EIAV) vaccine is the only attenuated lentiviral vaccine applied on a large scale that has been shown to be effective in controlling the prevalence of EIA in China. This vaccine was developed by successive passaging of a field-isolated virulent strain in different hosts and cultivated cells. To explore the molecular basis for the phenotype alteration of this vaccine strain, we systematically analyzed its genomic evolution during vaccine development. Results: Sequence analysis revealed that the genetic distance between the wild-type strain and six representative strains isolated from key development stages gradually increased with the number of passages. Env gene, but not gag and pol, showed a clear evolutionary flow similar to that of the whole genomes of different generations during the attenuation. Stable mutations were identified in multiple regions of multiple genes along with virus passaging. The adaption of the virus to the growth environment of cultured cells with accumulated genomic and genetic variations was positively correlated with the reduction in pathogenicity and rise of immunogenicity. Statistical analyses revealed significant differences in the frequency of the most stable mutations between in vivo and ex vivo-adapted strains and between virulent and attenuated strains. Conclusions: These data indicate that EIAV evolution during vaccine development generated an accumulation of mutations under the selective drive force, which helps to better understand the molecular basis of lentivirus pathogenicity and immunogenicity.
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Publication Date: 2016-02-03 PubMed ID: 26842878PubMed Central: PMC4738788DOI: 10.1186/s12977-016-0240-6Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explores the genetic evolution of the equine infectious anemia virus (EIAV) during the development of an attenuated vaccine. The researchers found that the virus underwent multiple mutations, particularly in the Env gene, reducing its pathogenicity and increasing its immunogenicity during the vaccine development period.

Research Process and Findings

  • The researchers analyzed the genomic evolution of the EIAV during its systematic attenuation to develop an effective vaccine. They collected samples at various stages of the development process and conducted a genomic sequence analysis on each.
  • The study revealed that the genetic distance increased between the wild-type strain and the six strains isolated at key developmental stages, as the number of passages increased. This suggests gradual genetic variation as a result of adaptation to their growth environment.
  • The Env gene, unlike the gag and pol genes, showed an evolutionary pattern similar to that of the entire genome during the attenuation process. This indicates the critical role of the Env gene in determining the phenotypic changes and its key role in immune response.
  • The research found stable mutations in multiple regions of multiple genes, demonstrating the versatile adaptability of the virus during its development. These mutations were correlated with a decrease in pathogenicity and an increase in immunogenicity.

Implications and Conclusions

  • Statistical analysis showed significant differences in the frequency of the most stable mutations. These differences were between in vivo and ex vivo adapted strains, and between virulent and attenuated strains. This signifies the potential influence of different growing conditions and characteristics of strains on the mutability of the virus.
  • The data gathered in the research indicates that the evolution of the EIAV during vaccine development caused a significant accumulation of mutations. This occurred under selective drive force, suggesting the strategic adaptation of the virus for survival and propagation.
  • Understanding the molecular basis of these mutations provides beneficial insights into the lentivirus’ pathogenicity and immunogenicity. This understanding can be used to guide future vaccine development strategies, especially for lentiviruses.

Cite This Article

APA
Wang XF, Lin YZ, Li Q, Liu Q, Zhao WW, Du C, Chen J, Wang X, Zhou JH. (2016). Genetic Evolution during the development of an attenuated EIAV vaccine. Retrovirology, 13, 9. https://doi.org/10.1186/s12977-016-0240-6

Publication

Retrovirology
ISSN: 1742-4690
NlmUniqueID: 101216893
Country: England
Language: English
Volume: 13
Pages: 9
PII: 9

Researcher Affiliations

Wang, Xue-Feng
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. xuefengwang1982@126.com.
  • Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China. xuefengwang1982@126.com.
Lin, Yue-Zhi
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. sndhr@163.com.
Li, Qiang
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. liqiang007200@sina.com.
  • Harbin Weike Biotechnology Development Company, Harbin, China. liqiang007200@sina.com.
Liu, Qiang
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. liuqiang_yyy@163.com.
Zhao, Wei-Wei
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. vivilnic@163.com.
Du, Cheng
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. chengdᦁ@163.com.
Chen, Jie
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. 18047113976@163.com.
Wang, Xiaojun
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. xjw@hvri.ac.cn.
Zhou, Jian-Hua
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. jianhua_uc@126.com.
  • Harbin Pharmaceutical Group Biovaccine Co., Harbin, 150069, China. jianhua_uc@126.com.

MeSH Terms

  • Animals
  • China
  • Equidae
  • Equine Infectious Anemia / prevention & control
  • Evolution, Molecular
  • Horses
  • Infectious Anemia Virus, Equine / genetics
  • Infectious Anemia Virus, Equine / immunology
  • Infectious Anemia Virus, Equine / pathogenicity
  • Molecular Sequence Data
  • Mutation
  • Sequence Analysis, DNA
  • Serial Passage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Vaccines, Attenuated / isolation & purification
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology
  • Viral Vaccines / isolation & purification

References

This article includes 28 references
  1. Koff WC, Johnson PR, Watkins DI, Burton DR, Lifson JD, Hasenkrug KJ, McDermott AB, Schultz A, Zamb TJ, Boyle R, Desrosiers RC. HIV vaccine design: insights from live attenuated SIV vaccines.. Nat Immunol 2006 Jan;7(1):19-23.
    doi: 10.1038/ni1296pubmed: 16357854google scholar: lookup
  2. Craigo JK, Ezzelarab C, Cook SJ, Liu C, Horohov D, Issel CJ, Montelaro RC. Protective efficacy of centralized and polyvalent envelope immunogens in an attenuated equine lentivirus vaccine.. PLoS Pathog 2015 Jan;11(1):e1004610.
    doi: 10.1371/journal.ppat.1004610pmc: PMC4287611pubmed: 25569288google scholar: lookup
  3. Craigo JK, Montelaro RC. Lessons in AIDS vaccine development learned from studies of equine infectious, anemia virus infection and immunity.. Viruses 2013 Dec 2;5(12):2963-76.
    doi: 10.3390/v5122963pmc: PMC3967156pubmed: 24316675google scholar: lookup
  4. Ma J, Shi N, Jiang CG, Lin YZ, Wang XF, Wang S, Lv XL, Zhao LP, Shao YM, Kong XG, Zhou JH, Shen RX. A proviral derivative from a reference attenuated EIAV vaccine strain failed to elicit protective immunity.. Virology 2011 Feb 5;410(1):96-106.
    doi: 10.1016/j.virol.2010.10.032pubmed: 21094511google scholar: lookup
  5. Lin YZ, Shen RX, Zhu ZY, Deng XL, Cao XZ, Wang XF, Ma J, Jiang CG, Zhao LP, Lv XL, Shao YM, Zhou JH. An attenuated EIAV vaccine strain induces significantly different immune responses from its pathogenic parental strain although with similar in vivo replication pattern.. Antiviral Res 2011 Nov;92(2):292-304.
    doi: 10.1016/j.antiviral.2011.08.016pubmed: 21893100google scholar: lookup
  6. Shen T, Liang H, Tong X, Fan X, He X, Ma Y, Xiang W, Shen R, Zhang X, Shao Y. Amino acid mutations of the infectious clone from Chinese EIAV attenuated vaccine resulted in reversion of virulence.. Vaccine 2006 Feb 6;24(6):738-49.
    doi: 10.1016/j.vaccine.2005.08.084pubmed: 16202485google scholar: lookup
  7. Ball JM, Swaggerty CL, Pei X, Lim WS, Xu X, Cox VC, Payne SL. SU proteins from virulent and avirulent EIAV demonstrate distinct biological properties.. Virology 2005 Mar 1;333(1):132-44.
    doi: 10.1016/j.virol.2004.12.022pubmed: 15708599google scholar: lookup
  8. Terme JM, Calvignac S, Duc Dodon M, Gazzolo L, Jordan A. E box motifs as mediators of proviral latency of human retroviruses.. Retrovirology 2009 Sep 16;6:81.
    doi: 10.1186/1742-4690-6-81pmc: PMC2749803pubmed: 19758443google scholar: lookup
  9. Miyazawa T, Tomonaga K, Kawaguchi Y, Kohmoto M, Inoshima Y, Maeda K, Mikami T, Maedadel K [corrected to Maeda K]. Effects of insertion of multiple AP-1 binding sites into the U3 region of the long terminal repeat of feline immunodeficiency virus.. Arch Virol 1994;139(1-2):37-48.
    doi: 10.1007/BF01309453pmc: PMC7086681pubmed: 7529991google scholar: lookup
  10. Pimkin M, Kossenkov AV, Mishra T, Morrissey CS, Wu W, Keller CA, Blobel GA, Lee D, Beer MA, Hardison RC, Weiss MJ. Divergent functions of hematopoietic transcription factors in lineage priming and differentiation during erythro-megakaryopoiesis.. Genome Res 2014 Dec;24(12):1932-44.
    doi: 10.1101/gr.164178.113pmc: PMC4248311pubmed: 25319996google scholar: lookup
  11. Jin S, Chen C, Montelaro RC. Equine infectious anemia virus Gag p9 function in early steps of virus infection and provirus production.. J Virol 2005 Jul;79(14):8793-801.
    doi: 10.1128/JVI.79.14.8793-8801.2005pmc: PMC1168773pubmed: 15994773google scholar: lookup
  12. Payne SL, Elder JH. The role of retroviral dUTPases in replication and virulence.. Curr Protein Pept Sci 2001 Dec;2(4):381-8.
    doi: 10.2174/1389203013381008pubmed: 12374097google scholar: lookup
  13. Liu L, Wan Y, Wu L, Sun J, Li H, Li H, Ma L, Shao Y. Broader HIV-1 neutralizing antibody responses induced by envelope glycoprotein mutants based on the EIAV attenuated vaccine.. Retrovirology 2010 Sep 1;7:71.
    doi: 10.1186/1742-4690-7-71pmc: PMC2940887pubmed: 20807451google scholar: lookup
  14. Tagmyer TL, Craigo JK, Cook SJ, Even DL, Issel CJ, Montelaro RC. Envelope determinants of equine infectious anemia virus vaccine protection and the effects of sequence variation on immune recognition.. J Virol 2008 Apr;82(8):4052-63.
    doi: 10.1128/JVI.02028-07pmc: PMC2292999pubmed: 18234792google scholar: lookup
  15. Li F, Craigo JK, Howe L, Steckbeck JD, Cook S, Issel C, Montelaro RC. A live attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses.. J Virol 2003 Jul;77(13):7244-53.
    doi: 10.1128/JVI.77.13.7244-7253.2003pmc: PMC164776pubmed: 12805423google scholar: lookup
  16. Liang H, He X, Shen RX, Shen T, Tong X, Ma Y, Xiang WH, Zhang XY, Shao YM. Combined amino acid mutations occurring in the envelope closely correlate with pathogenicity of EIAV.. Arch Virol 2006 Jul;151(7):1387-403.
    doi: 10.1007/s00705-005-0718-3pubmed: 16502285google scholar: lookup
  17. Vigerust DJ, Shepherd VL. Virus glycosylation: role in virulence and immune interactions.. Trends Microbiol 2007 May;15(5):211-8.
    doi: 10.1016/j.tim.2007.03.003pmc: PMC7127133pubmed: 17398101google scholar: lookup
  18. Han X, Zhang P, Wang X, Kong X, Xiang W, Zhou J. Construction of an Infectious Clone within the V3 Region of gp90 Surface Protein of EIAV by N- glycosylation Revers-mutations. Acta Veterinaria et Zootechnica Sinica 2008;39:1731–1736.
  19. Howe L, Leroux C, Issel CJ, Montelaro RC. Equine infectious anemia virus envelope evolution in vivo during persistent infection progressively increases resistance to in vitro serum antibody neutralization as a dominant phenotype.. J Virol 2002 Nov;76(21):10588-97.
    doi: 10.1128/JVI.76.21.10588-10597.2002pmc: PMC136617pubmed: 12368301google scholar: lookup
  20. Li H, Zhang X, Fan X, Shen T, Tong X, Shen R, Shao Y. A conservative domain shared by HIV gp120 and EIAV gp90: implications for HIV vaccine design.. AIDS Res Hum Retroviruses 2005 Dec;21(12):1057-9.
    doi: 10.1089/aid.2005.21.1057pubmed: 16379610google scholar: lookup
  21. Edlefsen PT, Rolland M, Hertz T, Tovanabutra S, Gartland AJ, deCamp AC, Magaret CA, Ahmed H, Gottardo R, Juraska M, McCoy C, Larsen BB, Sanders-Buell E, Carrico C, Menis S, Kijak GH, Bose M, Arroyo MA, O'Connell RJ, Nitayaphan S, Pitisuttithum P, Kaewkungwal J, Rerks-Ngarm S, Robb ML, Kirys T, Georgiev IS, Kwong PD, Scheffler K, Pond SL, Carlson JM, Michael NL, Schief WR, Mullins JI, Kim JH, Gilbert PB. Comprehensive sieve analysis of breakthrough HIV-1 sequences in the RV144 vaccine efficacy trial.. PLoS Comput Biol 2015 Feb;11(2):e1003973.
    doi: 10.1371/journal.pcbi.1003973pmc: PMC4315437pubmed: 25646817google scholar: lookup
  22. Du J, Wang X, Ma J, Wang J, Qin Y, Zhu C, Liu F, Shao Y, Zhou J, Qiao W, Liu X. Structural and biochemical insights into the V/I505T mutation found in the EIAV gp45 vaccine strain.. Retrovirology 2014 Mar 21;11:26.
    doi: 10.1186/1742-4690-11-26pmc: PMC3997929pubmed: 24656154google scholar: lookup
  23. Jiang CG, Gao X, Ma J, Lin YZ, Wang XF, Zhao LP, Hua YP, Liu D, Zhou JH. C-terminal truncation of the transmembrane protein of an attenuated lentiviral vaccine alters its in vitro but not in vivo replication and weakens its potential pathogenicity.. Virus Res 2011 Jun;158(1-2):235-45.
    doi: 10.1016/j.virusres.2011.04.007pubmed: 21539871google scholar: lookup
  24. Gao X, Jiang CG, Wang XF, Lin YZ, Ma J, Han XE, Zhao LP, Shen RX, Xiang WH, Zhou JH. Reverse mutation of the virulence-associated S2 gene does not cause an attenuated equine infectious anemia virus strain to revert to pathogenicity.. Virology 2013 Sep 1;443(2):321-8.
    doi: 10.1016/j.virol.2013.05.017pubmed: 23763769google scholar: lookup
  25. Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Wang F, Shen R, Kong X, Zhou J. Genomic comparison between attenuated Chinese equine infectious anemia virus vaccine strains and their parental virulent strains.. Arch Virol 2011 Feb;156(2):353-7.
    doi: 10.1007/s00705-010-0877-8pubmed: 21136127google scholar: lookup
  26. Qi X, Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Shen R, Wang F, Kong X, Su Z, Zhou J. Genomic analysis of an effective lentiviral vaccine-attenuated equine infectious anemia virus vaccine EIAV FDDV13.. Virus Genes 2010 Aug;41(1):86-98.
    doi: 10.1007/s11262-010-0491-6pubmed: 20526660google scholar: lookup
  27. Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 1999;41:95–98.
  28. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods.. Mol Biol Evol 2011 Oct;28(10):2731-9.
    doi: 10.1093/molbev/msr121pmc: PMC3203626pubmed: 21546353google scholar: lookup

Citations

This article has been cited 15 times.
  1. Wang XF, Zhang X, Ma W, Li J, Wang X. Host cell restriction factors of equine infectious anemia virus.. Virol Sin 2023 Aug;38(4):485-496.
    doi: 10.1016/j.virs.2023.07.001pubmed: 37419416google scholar: lookup
  2. Zhang X, Li J, Zhang M, Bai B, Ma W, Lin Y, Guo X, Wang XF, Wang X. A Novel, Fully Spliced, Accessory Gene in Equine Lentivirus with Distinct Rev-Responsive Element.. J Virol 2022 Sep 28;96(18):e0098622.
    doi: 10.1128/jvi.00986-22pubmed: 36069548google scholar: lookup
  3. Wang Y, Ma G, Wang XF, Na L, Guo X, Zhang J, Liu C, Du C, Qi T, Lin Y, Wang X. Keap1 recognizes EIAV early accessory protein Rev to promote antiviral defense.. PLoS Pathog 2022 Feb;18(2):e1009986.
    doi: 10.1371/journal.ppat.1009986pubmed: 35139135google scholar: lookup
  4. Wang XF, Wang YH, Bai B, Zhang M, Chen J, Zhang X, Gao M, Wang X. Truncation of the Cytoplasmic Tail of Equine Infectious Anemia Virus Increases Virion Production by Improving Env Cleavage and Plasma Membrane Localization.. J Virol 2021 Nov 9;95(23):e0108721.
    doi: 10.1128/JVI.01087-21pubmed: 34495693google scholar: lookup
  5. Romo-Sáenz CI, Tamez-Guerra P, Olivas-Holguin A, Ramos-Zayas Y, Obregón-Macías N, González-Ochoa G, Zavala-Díaz de la Serna FJ, Rodríguez-Padilla C, Tamez-Guerra R, Gomez-Flores R. Molecular detection of equine infectious anemia virus in clinically normal, seronegative horses in an endemic area of Mexico.. J Vet Diagn Invest 2021 Jul;33(4):758-761.
    doi: 10.1177/10406387211006195pubmed: 33797316google scholar: lookup
  6. Uversky VN. On the irrationality of rational design of an HIV vaccine in light of protein intrinsic disorder.. Arch Virol 2021 May;166(5):1283-1296.
    doi: 10.1007/s00705-021-04984-5pubmed: 33606110google scholar: lookup
  7. Câmara RJF, Bueno BL, Resende CF, Balasuriya UBR, Sakamoto SM, Reis JKPD. Viral Diseases that Affect Donkeys and Mules.. Animals (Basel) 2020 Nov 25;10(12).
    doi: 10.3390/ani10122203pubmed: 33255568google scholar: lookup
  8. Lin Y, Wang XF, Wang Y, Du C, Ren H, Liu C, Zhu D, Chen J, Na L, Liu D, Yang Z, Wang X. Env diversity-dependent protection of the attenuated equine infectious anaemia virus vaccine.. Emerg Microbes Infect 2020 Dec;9(1):1309-1320.
    doi: 10.1080/22221751.2020.1773323pubmed: 32525460google scholar: lookup
  9. Du C, Duan Y, Wang XF, Lin Y, Na L, Wang X, Chen K, Wang X. Attenuation of Equine Lentivirus Alters Mitochondrial Protein Expression Profile from Inflammation to Apoptosis.. J Virol 2019 Nov 1;93(21).
    doi: 10.1128/JVI.00653-19pubmed: 31391270google scholar: lookup
  10. Wang XF, Bai B, Lin Y, Qi T, Du C, Song M, Wang X. High-Efficiency Rescue of Equine Infectious Anemia Virus from a CMV-Driven Infectious Clone.. Virol Sin 2019 Dec;34(6):725-728.
    doi: 10.1007/s12250-019-00153-wpubmed: 31376080google scholar: lookup
  11. Alnaeem AA, Hemida MG. Surveillance of the equine infectious anemia virus in Eastern and Central Saudi Arabia during 2014-2016.. Vet World 2019 May;12(5):719-723.
    doi: 10.14202/vetworld.2019.719-723pubmed: 31327910google scholar: lookup
  12. Goh GK, Dunker AK, Foster JA, Uversky VN. HIV Vaccine Mystery and Viral Shell Disorder.. Biomolecules 2019 May 8;9(5).
    doi: 10.3390/biom9050178pubmed: 31072073google scholar: lookup
  13. Liu C, Wang XF, Wang Y, Chen J, Zhong Z, Lin Y, Wang X. Characterization of EIAV env Quasispecies during Long-Term Passage In Vitro: Gradual Loss of Pathogenicity.. Viruses 2019 Apr 24;11(4).
    doi: 10.3390/v11040380pubmed: 31022927google scholar: lookup
  14. Wang XF, Liu Q, Wang YH, Wang S, Chen J, Lin YZ, Ma J, Zhou JH, Wang X. Characterization of Equine Infectious Anemia Virus Long Terminal Repeat Quasispecies In Vitro and In Vivo.. J Virol 2018 Apr 15;92(8).
    doi: 10.1128/JVI.02150-17pubmed: 29386282google scholar: lookup
  15. Han X, Zhang P, Yu W, Xiang W, Li X. Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies.. Virus Genes 2016 Dec;52(6):814-822.
    doi: 10.1007/s11262-016-1382-2pubmed: 27572122google scholar: lookup
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