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Journal of virology2016; 90(16); 7405-7414; doi: 10.1128/JVI.00548-16

Assembly of Replication-Incompetent African Horse Sickness Virus Particles: Rational Design of Vaccines for All Serotypes.

Abstract: African horse sickness virus (AHSV), an orbivirus in the Reoviridae family with nine different serotypes, causes devastating disease in equids. The virion particle is composed of seven proteins organized in three concentric layers, an outer layer made of VP2 and VP5, a middle layer made of VP7, and inner layer made of VP3 that encloses a replicase complex of VP1, VP4, and VP6 and a genome of 10 double-stranded RNA segments. In this study, we sought to develop highly efficacious candidate vaccines against all AHSV serotypes, taking into account not only immunogenic and safety properties but also virus productivity and stability parameters, which are essential criteria for vaccine candidates. To achieve this goal, we first established a highly efficient reverse genetics (RG) system for AHSV serotype 1 (AHSV1) and, subsequently, a VP6-defective AHSV1 strain in combination with in trans complementation of VP6. This was then used to generate defective particles of all nine serotypes, which required the exchange of two to five RNA segments to achieve equivalent titers of particles. All reassortant-defective viruses could be amplified and propagated to high titers in cells complemented with VP6 but were totally incompetent in any other cells. Furthermore, these replication-incompetent AHSV particles were demonstrated to be highly protective against homologous virulent virus challenges in type I interferon receptor (IFNAR)-knockout mice. Thus, these defective viruses have the potential to be used for the development of safe and stable vaccine candidates. The RG system also provides a powerful tool for the study of the role of individual AHSV proteins in virus assembly, morphogenesis, and pathogenesis. African horse sickness virus is transmitted by biting midges and causes African horse sickness in equids, with mortality reaching up to 95% in naive horses. Therefore, the development of efficient vaccines is extremely important due to major economic losses in the equine industry. Through the establishment of a highly efficient RG system, replication-deficient viruses of all nine AHSV serotypes were generated. These defective viruses achieved high titers in a cell line complemented with VP6 but failed to propagate in wild-type mammalian or insect cells. Importantly, these candidate vaccine strains showed strong protective efficacy against AHSV infection in an IFNAR(-/-) mouse model.
Copyright © 2016 Lulla et al.
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Publication Date: 2016-07-27 PubMed ID: 27279609PubMed Central: PMC4984648DOI: 10.1128/JVI.00548-16Google Scholar: Lookup
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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.

The research article discusses the development of a vaccine for all serotypes of the African Horse Sickness Virus (AHSV), using a highly efficient reverse genetics system and replication-incompetent AHSV particles, which proved to be highly protective against challenges from the virus.

Objective

The objective of the study was to develop a vaccine against all AHSV serotypes. This was prompted by the devastating impact of the disease in equids, with mortality rates of up to 95% in naive horses. The researchers considered not just the immunogenic and safety properties of the vaccine candidates, but also their productivity and stability parameters.

Methodology

  • The researchers first established a highly effective reverse genetics (RG) system for AHSV serotype 1 (AHSV1).
  • A VP6-defective AHSV1 strain was developed, using a method of in trans complementation of VP6.
  • To generate defective particles of all nine serotypes, an exchange of two to five RNA segments was necessary. High titers of particles were achievable through this method.
  • All defective viruses produced could be amplified and propagated in cells complemented with VP6, but were not competent in any other cells.

Findings

  • The replication-incompetent AHSV particles were proven highly protective against challenges from the virulent virus, in type I interferon receptor (IFNAR)-knockout mice.
  • The researchers concluded that these defective viruses could be used in the formulation of safe and stable vaccine candidates.
  • Moreover, the RG system used offers a powerful tool for studying the role of individual AHSV proteins in virus assembly, morphogenesis, and pathogenesis.
  • The defective viruses achieved high titers in a cell line complemented with VP6 but didn’t propagate in wild-type mammalian or insect cells.
  • The potential vaccine strains demonstrated strong protective efficacy against AHSV infection in an IFNAR(-/-) mouse model.

Implications

AHSV is a widespread disease causing significant morbidity and mortality in horses. The development of a safe, effective, and stable vaccine against all serotypes of AHSV could prevent the devastating economic losses incurred by the equine industry due to the disease. The system used for development also provides a new method for studying the role and behavior of virus proteins.

Cite This Article

APA
Lulla V, Lulla A, Wernike K, Aebischer A, Beer M, Roy P. (2016). Assembly of Replication-Incompetent African Horse Sickness Virus Particles: Rational Design of Vaccines for All Serotypes. J Virol, 90(16), 7405-7414. https://doi.org/10.1128/JVI.00548-16

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 90
Issue: 16
Pages: 7405-7414

Researcher Affiliations

Lulla, Valeria
  • Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Lulla, Aleksei
  • Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Wernike, Kerstin
  • Institute of Diagnostic Virology, Friedrich-Loeffler Institut, Greifswald, Germany.
Aebischer, Andrea
  • Institute of Diagnostic Virology, Friedrich-Loeffler Institut, Greifswald, Germany.
Beer, Martin
  • Institute of Diagnostic Virology, Friedrich-Loeffler Institut, Greifswald, Germany.
Roy, Polly
  • Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom polly.roy@lshtm.ac.uk.

MeSH Terms

  • African Horse Sickness / prevention & control
  • African Horse Sickness Virus / genetics
  • African Horse Sickness Virus / immunology
  • African Horse Sickness Virus / physiology
  • Animals
  • Defective Viruses / genetics
  • Defective Viruses / immunology
  • Defective Viruses / physiology
  • Disease Models, Animal
  • Gene Deletion
  • Mice
  • Mice, Knockout
  • Reverse Genetics
  • Serogroup
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology
  • Viral Vaccines / metabolism
  • Virion / metabolism
  • Virus Assembly
  • Virus Replication

Grant Funding

  • BB/K015168/1 / Biotechnology and Biological Sciences Research Council

References

This article includes 39 references
  1. Mellor PS, Hamblin C. African horse sickness. Vet Res 35:445–466.
    doi: 10.1051/vetres:2004021pubmed: 15236676google scholar: lookup
  2. McVey DS, MacLachlan NJ. Vaccines for prevention of bluetongue and epizootic hemorrhagic disease in livestock: a North American perspective. Vector Borne Zoonotic Dis 15:385–396.
    doi: 10.1089/vbz.2014.1698pubmed: 26086559google scholar: lookup
  3. Iwata H, Yamagawa M, Roy P. Evolutionary relationships among the gnat-transmitted orbiviruses that cause African horse sickness, bluetongue, and epizootic hemorrhagic disease as evidenced by their capsid protein sequences. Virology 191:251–261.
    doi: 10.1016/0042-6822(92)90187-Tpubmed: 1329319google scholar: lookup
  4. Oura CA, Ivens PA, Bachanek-Bankowska K, Bin-Tarif A, Jallow DB, Sailleau C, Maan S, Mertens PC, Batten CA. African horse sickness in The Gambia: circulation of a live-attenuated vaccine-derived strain. Epidemiol Infect 140:462–465.
    doi: 10.1017/S095026881100080Xpubmed: 21733265google scholar: lookup
  5. Guthrie AJ, Quan M, Lourens CW, Audonnet JC, Minke JM, Yao J, He L, Nordgren R, Gardner IA, MacLachlan NJ. Protective immunization of horses with a recombinant canarypox virus vectored vaccine co-expressing genes encoding the outer capsid proteins of African horse sickness virus. Vaccine 27:4434–4438.
    doi: 10.1016/j.vaccine.2009.05.044pubmed: 19490959google scholar: lookup
  6. Kanai Y, van Rijn PA, Maris-Veldhuis M, Kaname Y, Athmaram TN, Roy P. Immunogenicity of recombinant VP2 proteins of all nine serotypes of African horse sickness virus. Vaccine 32:4932–4937.
    doi: 10.1016/j.vaccine.2014.07.031pmc: PMC4148702pubmed: 25045805google scholar: lookup
  7. van de Water SG, van Gennip RG, Potgieter CA, Wright IM, van Rijn PA. VP2 exchange and NS3/NS3a deletion in African horse sickness virus (AHSV) in development of disabled infectious single animal vaccine candidates for AHSV. J Virol 89:8764–8772.
    doi: 10.1128/JVI.01052-15pmc: PMC4524073pubmed: 26063433google scholar: lookup
  8. Roy P, Bishop DH, Howard S, Aitchison H, Erasmus B. Recombinant baculovirus-synthesized African horsesickness virus (AHSV) outer-capsid protein VP2 provides protection against virulent AHSV challenge. J Gen Virol 77(Pt 9):2053–2057.
    doi: 10.1099/0022-1317-77-9-2053pubmed: 8811002google scholar: lookup
  9. Scanlen M, Paweska JT, Verschoor JA, van Dijk AA. The protective efficacy of a recombinant VP2-based African horsesickness subunit vaccine candidate is determined by adjuvant. Vaccine 20:1079–1088.
    doi: 10.1016/S0264-410X(01)00445-5pubmed: 11803068google scholar: lookup
  10. Alberca B, Bachanek-Bankowska K, Cabana M, Calvo-Pinilla E, Viaplana E, Frost L, Gubbins S, Urniza A, Mertens P, Castillo-Olivares J. Vaccination of horses with a recombinant modified vaccinia Ankara virus (MVA) expressing African horse sickness (AHS) virus major capsid protein VP2 provides complete clinical protection against challenge. Vaccine 32:3670–3674.
    doi: 10.1016/j.vaccine.2014.04.036pmc: PMC4061461pubmed: 24837765google scholar: lookup
  11. Roy P. Orbivirus structure and assembly. Virology 216:1–11.
    doi: 10.1006/viro.1996.0028pubmed: 8614976google scholar: lookup
  12. Iwata H, Chuma T, Roy P. Characterization of the genes encoding two of the major capsid proteins of epizootic haemorrhagic disease virus indicates a close genetic relationship to bluetongue virus. J Gen Virol 73:915–924.
    doi: 10.1099/0022-1317-73-4-915pubmed: 1321879google scholar: lookup
  13. Zhang X, Boyce M, Bhattacharya B, Schein S, Roy P, Zhou ZH. Bluetongue virus coat protein VP2 contains sialic acid-binding domains, and VP5 resembles enveloped virus fusion proteins. Proc Natl Acad Sci U S A 107:6292–6297.
    doi: 10.1073/pnas.0913403107pmc: PMC2852009pubmed: 20332209google scholar: lookup
  14. Zhang X, Patel A, Celma CC, Yu X, Roy P, Zhou ZH. Atomic model of a nonenveloped virus reveals pH sensors for a coordinated process of cell entry. Nat Struct Mol Biol 23:74–80.
    doi: 10.1038/nsmb.3134pmc: PMC5669276pubmed: 26641711google scholar: lookup
  15. Manole V, Laurinmaki P, Van Wyngaardt W, Potgieter CA, Wright IM, Venter GJ, van Dijk AA, Sewell BT, Butcher SJ. Structural insight into African horsesickness virus infection. J Virol 86:7858–7866.
    doi: 10.1128/JVI.00517-12pmc: PMC3421665pubmed: 22593166google scholar: lookup
  16. Basak AK, Gouet P, Grimes J, Roy P, Stuart D. Crystal structure of the top domain of African horse sickness virus VP7: comparisons with bluetongue virus VP7. J Virol 70:3797–3806.
    pmc: PMC190256pubmed: 8648715
  17. Boyce M, Celma CC, Roy P. Development of reverse genetics systems for bluetongue virus: recovery of infectious virus from synthetic RNA transcripts. J Virol 82:8339–8348.
    doi: 10.1128/JVI.00808-08pmc: PMC2519640pubmed: 18562540google scholar: lookup
  18. Matsuo E, Roy P. Bluetongue virus VP6 acts early in the replication cycle and can form the basis of chimeric virus formation. J Virol 83:8842–8848.
    doi: 10.1128/JVI.00465-09pmc: PMC2738189pubmed: 19553329google scholar: lookup
  19. van Gennip RG, van de Water SG, Potgieter CA, Wright IM, Veldman D, van Rijn PA. Rescue of recent virulent and avirulent field strains of bluetongue virus by reverse genetics. PLoS One 7:e30540.
    doi: 10.1371/journal.pone.0030540pmc: PMC3281837pubmed: 22363444google scholar: lookup
  20. Janowicz A, Caporale M, Shaw A, Gulletta S, Di Gialleonardo L, Ratinier M, Palmarini M. Multiple genome segments determine virulence of bluetongue virus serotype 8. J Virol 89:5238–5249.
    doi: 10.1128/JVI.00395-15pmc: PMC4442542pubmed: 25822026google scholar: lookup
  21. Nunes SF, Hamers C, Ratinier M, Shaw A, Brunet S, Hudelet P, Palmarini M. A synthetic biology approach for a vaccine platform against known and newly emerging serotypes of bluetongue virus. J Virol 88:12222–12232.
    doi: 10.1128/JVI.02183-14pmc: PMC4248921pubmed: 25142610google scholar: lookup
  22. Matsuo E, Celma CC, Boyce M, Viarouge C, Sailleau C, Dubois E, Breard E, Thiery R, Zientara S, Roy P. Generation of replication-defective virus-based vaccines that confer full protection in sheep against virulent bluetongue virus challenge. J Virol 85:10213–10221.
    doi: 10.1128/JVI.05412-11pmc: PMC3196398pubmed: 21795358google scholar: lookup
  23. Kaname Y, Celma CC, Kanai Y, Roy P. Recovery of African horse sickness virus from synthetic RNA. J Gen Virol 94:2259–2265.
    doi: 10.1099/vir.0.055905-0pubmed: 23860489google scholar: lookup
  24. Matsuo E, Celma CC, Roy P. A reverse genetics system of African horse sickness virus reveals existence of primary replication. FEBS Lett 584:3386–3391.
    doi: 10.1016/j.febslet.2010.06.030pubmed: 20600010google scholar: lookup
  25. Celma CC, Boyce M, van Rijn PA, Eschbaumer M, Wernike K, Hoffmann B, Beer M, Haegeman A, De Clercq K, Roy P. Rapid generation of replication-deficient monovalent and multivalent vaccines for bluetongue virus: protection against virulent virus challenge in cattle and sheep. J Virol 87:9856–9864.
    doi: 10.1128/JVI.01514-13pmc: PMC3754119pubmed: 23824810google scholar: lookup
  26. Wechsler SJ, McHolland LE, Tabachnick WJ. Cell lines from Culicoides variipennis (Diptera: Ceratopogonidae) support replication of bluetongue virus. J Invertebr Pathol 54:385–393.
    doi: 10.1016/0022-2011(89)90123-7pubmed: 2553822google scholar: lookup
  27. Castillo-Olivares J, Calvo-Pinilla E, Casanova I, Bachanek-Bankowska K, Chiam R, Maan S, Nieto JM, Ortego J, Mertens PP. A modified vaccinia Ankara virus (MVA) vaccine expressing African horse sickness virus (AHSV) VP2 protects against AHSV challenge in an IFNAR−/− mouse model. PLoS One 6:e16503.
    doi: 10.1371/journal.pone.0016503pmc: PMC3027694pubmed: 21298069google scholar: lookup
  28. Quan M, Lourens CW, MacLachlan NJ, Gardner IA, Guthrie AJ. Development and optimisation of a duplex real-time reverse transcription quantitative PCR assay targeting the VP7 and NS2 genes of African horse sickness virus. J Virol Methods 167:45–52.
    doi: 10.1016/j.jviromet.2010.03.009pubmed: 20304015google scholar: lookup
  29. Toussaint JF, Sailleau C, Breard E, Zientara S, De Clercq K. Bluetongue virus detection by two real-time RT-qPCRs targeting two different genomic segments. J Virol Methods 140:115–123.
    doi: 10.1016/j.jviromet.2006.11.007pubmed: 17196266google scholar: lookup
  30. Matsuo E, Leon E, Matthews SJ, Roy P. Structure based modification of bluetongue virus helicase protein VP6 to produce a viable VP6-truncated BTV. Biochem Biophys Res Commun 451:603–608.
    doi: 10.1016/j.bbrc.2014.08.028pmc: PMC4169673pubmed: 25128829google scholar: lookup
  31. Ratinier M, Caporale M, Golder M, Franzoni G, Allan K, Nunes SF, Armezzani A, Bayoumy A, Rixon F, Shaw A, Palmarini M. Identification and characterization of a novel non-structural protein of bluetongue virus. PLoS Pathog 7:e1002477.
    doi: 10.1371/journal.ppat.1002477pmc: PMC3248566pubmed: 22241985google scholar: lookup
  32. MacLachlan NJ, Guthrie AJ. Re-emergence of bluetongue, African horse sickness, and other orbivirus diseases. Vet Res 41:35.
    doi: 10.1051/vetres/2010007pmc: PMC2826768pubmed: 20167199google scholar: lookup
  33. Matsuo E, Roy P. Minimum requirements for bluetongue virus primary replication in vivo. J Virol 87:882–889.
    doi: 10.1128/JVI.02363-12pmc: PMC3554043pubmed: 23115294google scholar: lookup
  34. Li H, Zhou R, Chen J, Tian X, Zhang Q, Zeng Q, Gong S. A recombinant replication-defective human adenovirus type 3: a vaccine candidate. Vaccine 27:116–122.
    doi: 10.1016/j.vaccine.2008.10.032pubmed: 18977265google scholar: lookup
  35. Wirblich C, Bhattacharya B, Roy P. Nonstructural protein 3 of bluetongue virus assists virus release by recruiting ESCRT-I protein Tsg101. J Virol 80:460–473.
    doi: 10.1128/JVI.80.1.460-473.2006pmc: PMC1317520pubmed: 16352570google scholar: lookup
  36. Sung P-Y, Roy P. Sequential packaging of RNA genomic segments during the assembly of bluetongue virus. Nucleic Acids Res 42:13824–13838.
    doi: 10.1093/nar/gkᅱpmc: PMC4267631pubmed: 25428366google scholar: lookup
  37. Celma CC, Roy P. A viral nonstructural protein regulates bluetongue virus trafficking and release. J Virol 83:6806–6816.
    doi: 10.1128/JVI.00263-09pmc: PMC2698550pubmed: 19369335google scholar: lookup
  38. Jimenez-Guardeno JM, Regla-Nava JA, Nieto-Torres JL, DeDiego ML, Castano-Rodriguez C, Fernandez-Delgado R, Perlman S, Enjuanes L. Identification of the mechanisms causing reversion to virulence in an attenuated SARS-CoV for the design of a genetically stable vaccine. PLoS Pathog 11:e1005215.
    doi: 10.1371/journal.ppat.1005215pmc: PMC4626112pubmed: 26513244google scholar: lookup
  39. Dudek T, Knipe DM. Replication-defective viruses as vaccines and vaccine vectors. Virology 344:230–239.
    doi: 10.1016/j.virol.2005.09.020pubmed: 16364753google scholar: lookup

Citations

This article has been cited 15 times.
  1. Stewart H, Lu Y, O'Keefe S, Valpadashi A, Cruz-Zaragoza LD, Michel HA, Nguyen SK, Carnell GW, Lukhovitskaya N, Milligan R, Adewusi Y, Jungreis I, Lulla V, Matthews DA, High S, Rehling P, Emmott E, Heeney JL, Davidson AD, Edgar JR, Smith GL, Firth AE. The SARS-CoV-2 protein ORF3c is a mitochondrial modulator of innate immunity. iScience 2023 Nov 17;26(11):108080.
    doi: 10.1016/j.isci.2023.108080pubmed: 37860693google scholar: lookup
  2. Bekker S, Potgieter CA, van Staden V, Theron J. Investigating the Role of African Horse Sickness Virus VP7 Protein Crystalline Particles on Virus Replication and Release. Viruses 2022 Oct 4;14(10).
    doi: 10.3390/v14102193pubmed: 36298748google scholar: lookup
  3. Bekker S, Huismans H, van Staden V. Generation of a Soluble African Horse Sickness Virus VP7 Protein Capable of Forming Core-like Particles. Viruses 2022 Jul 26;14(8).
    doi: 10.3390/v14081624pubmed: 35893692google scholar: lookup
  4. Fairbanks EL, Brennan ML, Mertens PPC, Tildesley MJ, Daly JM. Re-parameterization of a mathematical model of African horse sickness virus using data from a systematic literature search. Transbound Emerg Dis 2022 Jul;69(4):e671-e681.
    doi: 10.1111/tbed.14420pubmed: 34921513google scholar: lookup
  5. Sullivan E, Lecollinet S, Kerviel A, Hue E, Pronost S, Beck C, Dumarest M, Zientara S, Roy P. Entry-competent-replication-abortive African horse sickness virus strains elicit robust immunity in ponies against all serotypes. Vaccine 2021 May 27;39(23):3161-3168.
    doi: 10.1016/j.vaccine.2021.04.034pubmed: 33958224google scholar: lookup
  6. Lulla V, Firth AE. A hidden gene in astroviruses encodes a viroporin. Nat Commun 2020 Aug 13;11(1):4070.
    doi: 10.1038/s41467-020-17906-xpubmed: 32792502google scholar: lookup
  7. Calvo-Pinilla E, Marín-López A, Utrilla-Trigo S, Jiménez-Cabello L, Ortego J. Reverse genetics approaches: a novel strategy for African horse sickness virus vaccine design. Curr Opin Virol 2020 Oct;44:49-56.
    doi: 10.1016/j.coviro.2020.06.003pubmed: 32659516google scholar: lookup
  8. Rutkowska DA, Mokoena NB, Tsekoa TL, Dibakwane VS, O'Kennedy MM. Plant-produced chimeric virus-like particles - a new generation vaccine against African horse sickness. BMC Vet Res 2019 Dec 3;15(1):432.
    doi: 10.1186/s12917-019-2184-2pubmed: 31796116google scholar: lookup
  9. Dennis SJ, Meyers AE, Hitzeroth II, Rybicki EP. African Horse Sickness: A Review of Current Understanding and Vaccine Development. Viruses 2019 Sep 11;11(9).
    doi: 10.3390/v11090844pubmed: 31514299google scholar: lookup
  10. Marín-Lopez A, Calvo-Pinilla E, Moreno S, Utrilla-Trigo S, Nogales A, Brun A, Fikrig E, Ortego J. Modeling Arboviral Infection in Mice Lacking the Interferon Alpha/Beta Receptor. Viruses 2019 Jan 8;11(1).
    doi: 10.3390/v11010035pubmed: 30625992google scholar: lookup
  11. Lulla V, Dinan AM, Hosmillo M, Chaudhry Y, Sherry L, Irigoyen N, Nayak KM, Stonehouse NJ, Zilbauer M, Goodfellow I, Firth AE. An upstream protein-coding region in enteroviruses modulates virus infection in gut epithelial cells. Nat Microbiol 2019 Feb;4(2):280-292.
    doi: 10.1038/s41564-018-0297-1pubmed: 30478287google scholar: lookup
  12. Aksular M, Calvo-Pinilla E, Marín-López A, Ortego J, Chambers AC, King LA, Castillo-Olivares J. A single dose of African horse sickness virus (AHSV) VP2 based vaccines provides complete clinical protection in a mouse model. Vaccine 2018 Nov 12;36(46):7003-7010.
    doi: 10.1016/j.vaccine.2018.09.065pubmed: 30309744google scholar: lookup
  13. Dennis SJ, Meyers AE, Guthrie AJ, Hitzeroth II, Rybicki EP. Immunogenicity of plant-produced African horse sickness virus-like particles: implications for a novel vaccine. Plant Biotechnol J 2018 Feb;16(2):442-450.
    doi: 10.1111/pbi.12783pubmed: 28650085google scholar: lookup
  14. Lulla V, Losada A, Lecollinet S, Kerviel A, Lilin T, Sailleau C, Beck C, Zientara S, Roy P. Protective efficacy of multivalent replication-abortive vaccine strains in horses against African horse sickness virus challenge. Vaccine 2017 Jul 24;35(33):4262-4269.
    doi: 10.1016/j.vaccine.2017.06.023pubmed: 28625521google scholar: lookup
  15. Fajardo T Jr, AlShaikhahmed K, Roy P. Generation of infectious RNA complexes in Orbiviruses: RNA-RNA interactions of genomic segments. Oncotarget 2016 Nov 8;7(45):72559-72570.
    doi: 10.18632/oncotarget.12496pubmed: 27736800google scholar: lookup
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