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Home / Equine Research Bank / J Virol / Venezuelan equine encephalitis replicon particles can induce...
Journal of virology2013; 87(10); 5447-5460; doi: 10.1128/JVI.03462-12

Venezuelan equine encephalitis replicon particles can induce rapid protection against foot-and-mouth disease virus.

Abstract: We have previously shown that delivery of the porcine type I interferon gene (poIFN-α/β) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the applicability of such a control strategy in the livestock industry. Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRPs) can induce rapid protection of mice against either homologous or, in some cases, heterologous virus challenge. As an alternative approach to induce rapid protection against FMDV, we have examined the ability of VRPs containing either the gene for green fluorescent protein (VRP-GFP) or poIFN-α (VRP-poIFN-α) to block FMDV replication in vitro and in vivo. Pretreatment of swine or bovine cell lines with either VRP significantly inhibited subsequent infection with FMDV as early as 6 h after treatment and for at least 120 h posttreatment. Furthermore, mice pretreated with either 10(7) or 10(8) infectious units of VRP-GFP and challenged with a lethal dose of FMDV 24 h later were protected from death. Protection was induced as early as 6 h after treatment and lasted for at least 48 h and correlated with induction of an antiviral response and production of IFN-α. By 6 h after treatment several genes were upregulated, and the number of genes and the level of induction increased at 24 h. Finally, we demonstrated that the chemokine IP-10, which is induced by IFN-α and VRP-GFP, is directly involved in protection against FMDV.
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Publication Date: 2013-03-06 PubMed ID: 23468490PubMed Central: PMC3648198DOI: 10.1128/JVI.03462-12Google Scholar: Lookup
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  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

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 centers on the use of Venezuelan equine encephalitis virus and its potential to rapidly protect against foot-and-mouth disease virus (FMDV) in livestock.

Objective

The primary objective of this study is to explore alternative means to rapidly protect against FMDV. Previously, the scientists delivered the porcine type I interferon gene (poIFN-α/β) using a human adenovirus vector to protect swine. However, the high doses needed limited its commercial application. This led them to investigate the use of Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRP).

Methodology

  • The researchers used VRP containing either the gene for green fluorescent protein (VRP-GFP) or poIFN-α (VRP-poIFN-α).
  • In vitro and in vivo tests were conducted to examine the ability of VRPs to halt FMDV replication.
  • These VRPs were used as a pretreatment on bovine and swine cell lines.
  • The FMDV infection was significantly stymied post-treatment, up to 120 hours.

Results

  • Mice pretreated with VRPs were protected from death when they were challenged with a lethal dose of FMDV 24 hours later.
  • Protection was noticed as early as 6 hours after treatment and it lasted for at least 48 hours.
  • The protection was found to be linked with the initiation of an antiviral response and production of IFN-α.
  • A number of genes were upregulated 6 hours after the treatment. Both the number of upregulated genes and the actual upregulation level increased at 24 hours.

Significant Findings

The study concluded that the chemokine IP-10, which is brought on by IFN-α and VRP-GFP, plays a vital role in protection against FMDV. The rapid protection provided by VRP could provide a valuable alternative or addition to vaccination programs in efforts to control FMDV.

Cite This Article

APA
Diaz-San Segundo F, Dias CC, Moraes MP, Weiss M, Perez-Martin E, Owens G, Custer M, Kamrud K, de los Santos T, Grubman MJ. (2013). Venezuelan equine encephalitis replicon particles can induce rapid protection against foot-and-mouth disease virus. J Virol, 87(10), 5447-5460. https://doi.org/10.1128/JVI.03462-12

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 87
Issue: 10
Pages: 5447-5460

Researcher Affiliations

Diaz-San Segundo, Fayna
  • Plum Island Animal Disease Center, North Atlantic Area, Agricultural Research Service, US Department of Agriculture, Greenport, New York, USA.
Dias, Camila C A
    Moraes, Mauro P
      Weiss, Marcelo
        Perez-Martin, Eva
          Owens, Gary
            Custer, Max
              Kamrud, Kurt
                de los Santos, Teresa
                  Grubman, Marvin J

                    MeSH Terms

                    • Animals
                    • Disease Models, Animal
                    • Encephalitis Virus, Venezuelan Equine / genetics
                    • Foot-and-Mouth Disease / immunology
                    • Foot-and-Mouth Disease / prevention & control
                    • Foot-and-Mouth Disease Virus / immunology
                    • Genetic Therapy / methods
                    • Genetic Vectors
                    • Interferon-alpha / genetics
                    • Interferon-alpha / immunology
                    • Mice
                    • Mice, Inbred C57BL
                    • Survival Analysis

                    References

                    This article includes 41 references
                    1. Grubman MJ, Baxt B. Foot-and-mouth disease.. Clin Microbiol Rev 2004 Apr;17(2):465-93.
                      pmc: PMC387408pubmed: 15084510doi: 10.1128/cmr.17.2.465-493.2004google scholar: lookup
                    2. Domingo E, Escarmís C, Baranowski E, Ruiz-Jarabo CM, Carrillo E, Núñez JI, Sobrino F. Evolution of foot-and-mouth disease virus.. Virus Res 2003 Jan;91(1):47-63.
                      pubmed: 12527437doi: 10.1016/s0168-1702(02)00259-9google scholar: lookup
                    3. Golde WT, Pacheco JM, Duque H, Doel T, Penfold B, Ferman GS, Gregg DR, Rodriguez LL. Vaccination against foot-and-mouth disease virus confers complete clinical protection in 7 days and partial protection in 4 days: Use in emergency outbreak response.. Vaccine 2005 Dec 30;23(50):5775-82.
                      pubmed: 16153756doi: 10.1016/j.vaccine.2005.07.043google scholar: lookup
                    4. Moraes MP, Chinsangaram J, Brum MC, Grubman MJ. Immediate protection of swine from foot-and-mouth disease: a combination of adenoviruses expressing interferon alpha and a foot-and-mouth disease virus subunit vaccine.. Vaccine 2003 Dec 12;22(2):268-79.
                      pubmed: 14615155doi: 10.1016/s0264-410x(03)00560-7google scholar: lookup
                    5. Pacheco JM, Brum MC, Moraes MP, Golde WT, Grubman MJ. Rapid protection of cattle from direct challenge with foot-and-mouth disease virus (FMDV) by a single inoculation with an adenovirus-vectored FMDV subunit vaccine.. Virology 2005 Jul 5;337(2):205-9.
                      pubmed: 15893355doi: 10.1016/j.virol.2005.04.014google scholar: lookup
                    6. Chinsangaram J, Koster M, Grubman MJ. Inhibition of L-deleted foot-and-mouth disease virus replication by alpha/beta interferon involves double-stranded RNA-dependent protein kinase.. J Virol 2001 Jun;75(12):5498-503.
                      pmc: PMC114262pubmed: 11356957doi: 10.1128/jvi.75.12.5498-5503.2001google scholar: lookup
                    7. Moraes MP, de Los Santos T, Koster M, Turecek T, Wang H, Andreyev VG, Grubman MJ. Enhanced antiviral activity against foot-and-mouth disease virus by a combination of type I and II porcine interferons.. J Virol 2007 Jul;81(13):7124-35.
                      pmc: PMC1933294pubmed: 17459931doi: 10.1128/jvi.02775-06google scholar: lookup
                    8. Díaz-San Segundo F, Weiss M, Perez-Martín E, Koster MJ, Zhu J, Grubman MJ, de los Santos T. Antiviral activity of bovine type III interferon against foot-and-mouth disease virus.. Virology 2011 May 10;413(2):283-92.
                      pubmed: 21435672doi: 10.1016/j.virol.2011.02.023google scholar: lookup
                    9. Chinsangaram J, Moraes MP, Koster M, Grubman MJ. Novel viral disease control strategy: adenovirus expressing alpha interferon rapidly protects swine from foot-and-mouth disease.. J Virol 2003 Jan;77(2):1621-5.
                      pmc: PMC140819pubmed: 12502879doi: 10.1128/jvi.77.2.1621-1625.2003google scholar: lookup
                    10. Dias CC, Moraes MP, Segundo FD, de los Santos T, Grubman MJ. Porcine type I interferon rapidly protects swine against challenge with multiple serotypes of foot-and-mouth disease virus.. J Interferon Cytokine Res 2011 Feb;31(2):227-36.
                      pubmed: 20874428doi: 10.1089/jir.2010.0055google scholar: lookup
                    11. Wu Q, Brum MC, Caron L, Koster M, Grubman MJ. Adenovirus-mediated type I interferon expression delays and reduces disease signs in cattle challenged with foot-and-mouth disease virus.. J Interferon Cytokine Res 2003 Jul;23(7):359-68.
                      pubmed: 14511462doi: 10.1089/107999003322226014google scholar: lookup
                    12. Perez-Martin E, Weiss M, Diaz-San Segundo F, Pacheco JM, Arzt J, Grubman MJ, de los Santos T. Bovine type III interferon significantly delays and reduces the severity of foot-and-mouth disease in cattle.. J Virol 2012 Apr;86(8):4477-87.
                      pmc: PMC3318609pubmed: 22301155doi: 10.1128/jvi.06683-11google scholar: lookup
                    13. Medzhitov R, Janeway CA Jr. Innate immune recognition and control of adaptive immune responses.. Semin Immunol 1998 Oct;10(5):351-3.
                      pubmed: 9799709doi: 10.1006/smim.1998.0136google scholar: lookup
                    14. Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors.. Nat Rev Immunol 2006 Sep;6(9):644-58.
                      pubmed: 16932750doi: 10.1038/nri1900google scholar: lookup
                    15. Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity.. Immunity 2011 May 27;34(5):637-50.
                      pubmed: 21616434doi: 10.1016/j.immuni.2011.05.006google scholar: lookup
                    16. Pushko P, Parker M, Ludwig GV, Davis NL, Johnston RE, Smith JF. Replicon-helper systems from attenuated Venezuelan equine encephalitis virus: expression of heterologous genes in vitro and immunization against heterologous pathogens in vivo.. Virology 1997 Dec 22;239(2):389-401.
                      pubmed: 9434729doi: 10.1006/viro.1997.8878google scholar: lookup
                    17. Lee JS, Hadjipanayis AG, Welkos SL. Venezuelan equine encephalitis virus-vectored vaccines protect mice against anthrax spore challenge.. Infect Immun 2003 Mar;71(3):1491-6.
                      pmc: PMC148867pubmed: 12595467doi: 10.1128/iai.71.3.1491-1496.2003google scholar: lookup
                    18. Hooper JW, Ferro AM, Golden JW, Silvera P, Dudek J, Alterson K, Custer M, Rivers B, Morris J, Owens G, Smith JF, Kamrud KI. Molecular smallpox vaccine delivered by alphavirus replicons elicits protective immunity in mice and non-human primates.. Vaccine 2009 Dec 11;28(2):494-511.
                      pmc: PMC2789203pubmed: 19833247doi: 10.1016/j.vaccine.2009.09.133google scholar: lookup
                    19. Konopka JL, Penalva LO, Thompson JM, White LJ, Beard CW, Keene JD, Johnston RE. A two-phase innate host response to alphavirus infection identified by mRNP-tagging in vivo.. PLoS Pathog 2007 Dec;3(12):e199.
                      doi: 10.1371/journal.ppat.0030199pmc: PMC2151086pubmed: 18215114google scholar: lookup
                    20. Konopka JL, Thompson JM, Whitmore AC, Webb DL, Johnston RE. Acute infection with venezuelan equine encephalitis virus replicon particles catalyzes a systemic antiviral state and protects from lethal virus challenge.. J Virol 2009 Dec;83(23):12432-42.
                      pmc: PMC2786707pubmed: 19793821doi: 10.1128/jvi.00564-09google scholar: lookup
                    21. Swaney LM. A continuous bovine kidney cell line for routine assays of foot-and-mouth disease virus.. Vet Microbiol 1988 Sep;18(1):1-14.
                      pubmed: 2847400doi: 10.1016/0378-1135(88)90111-3google scholar: lookup
                    22. Graham FL, Prevec L. Manipulation of adenovirus vectors.. Methods Mol Biol 1991;7:109-28.
                      pubmed: 21416352doi: 10.1385/0-89603-178-0:109google scholar: lookup
                    23. Kinney RM, Johnson BJ, Welch JB, Tsuchiya KR, Trent DW. The full-length nucleotide sequences of the virulent Trinidad donkey strain of Venezuelan equine encephalitis virus and its attenuated vaccine derivative, strain TC-83.. Virology 1989 May;170(1):19-30.
                      pubmed: 2524126doi: 10.1016/0042-6822(89)90347-4google scholar: lookup
                    24. Bernstein DI, Reap EA, Katen K, Watson A, Smith K, Norberg P, Olmsted RA, Hoeper A, Morris J, Negri S, Maughan MF, Chulay JD. Randomized, double-blind, Phase 1 trial of an alphavirus replicon vaccine for cytomegalovirus in CMV seronegative adult volunteers.. Vaccine 2009 Dec 11;28(2):484-93.
                      pubmed: 19857446doi: 10.1016/j.vaccine.2009.09.135google scholar: lookup
                    25. Kamrud KI, Custer M, Dudek JM, Owens G, Alterson KD, Lee JS, Groebner JL, Smith JF. Alphavirus replicon approach to promoterless analysis of IRES elements.. Virology 2007 Apr 10;360(2):376-87.
                      pmc: PMC1885372pubmed: 17156813doi: 10.1016/j.virol.2006.10.049google scholar: lookup
                    26. Moraes MP, Mayr GA, Grubman MJ. pAd5-Blue: direct ligation system for engineering recombinant adenovirus constructs.. Biotechniques 2001 Nov;31(5):1050, 1052, 1054-6.
                      pubmed: 11730012doi: 10.2144/01315st05google scholar: lookup
                    27. Moraes MP, Mayr GA, Mason PW, Grubman MJ. Early protection against homologous challenge after a single dose of replication-defective human adenovirus type 5 expressing capsid proteins of foot-and-mouth disease virus (FMDV) strain A24.. Vaccine 2002 Feb 22;20(11-12):1631-9.
                      pubmed: 11858872doi: 10.1016/s0264-410x(01)00483-2google scholar: lookup
                    28. de Los Santos T, de Avila Botton S, Weiblen R, Grubman MJ. The leader proteinase of foot-and-mouth disease virus inhibits the induction of beta interferon mRNA and blocks the host innate immune response.. J Virol 2006 Feb;80(4):1906-14.
                      pmc: PMC1367153pubmed: 16439546doi: 10.1128/jvi.80.4.1906-1914.2006google scholar: lookup
                    29. Dias CC, Moraes MP, Weiss M, Diaz-San Segundo F, Perez-Martin E, Salazar AM, de los Santos T, Grubman MJ. Novel antiviral therapeutics to control foot-and-mouth disease.. J Interferon Cytokine Res 2012 Oct;32(10):462-73.
                      pubmed: 22924938doi: 10.1089/jir.2012.0012google scholar: lookup
                    30. . User bulletin 2. ABI Prism 7700 sequence detection system: relative quantification of gene expression (P/N 4303859). Applied Biosystems 1997.
                    31. Georgel P, Jiang Z, Kunz S, Janssen E, Mols J, Hoebe K, Bahram S, Oldstone MB, Beutler B. Vesicular stomatitis virus glycoprotein G activates a specific antiviral Toll-like receptor 4-dependent pathway.. Virology 2007 Jun 5;362(2):304-13.
                      pubmed: 17292937doi: 10.1016/j.virol.2006.12.032google scholar: lookup
                    32. Salguero FJ, Sánchez-Martín MA, Díaz-San Segundo F, de Avila A, Sevilla N. Foot-and-mouth disease virus (FMDV) causes an acute disease that can be lethal for adult laboratory mice.. Virology 2005 Feb 5;332(1):384-96.
                      pubmed: 15661169doi: 10.1016/j.virol.2004.11.005google scholar: lookup
                    33. Diaz-San Segundo F, Moraes MP, de Los Santos T, Dias CC, Grubman MJ. Interferon-induced protection against foot-and-mouth disease virus infection correlates with enhanced tissue-specific innate immune cell infiltration and interferon-stimulated gene expression.. J Virol 2010 Feb;84(4):2063-77.
                      pmc: PMC2812365pubmed: 19955313doi: 10.1128/jvi.01874-09google scholar: lookup
                    34. Abe T, Takahashi H, Hamazaki H, Miyano-Kurosaki N, Matsuura Y, Takaku H. Baculovirus induces an innate immune response and confers protection from lethal influenza virus infection in mice.. J Immunol 2003 Aug 1;171(3):1133-9.
                      pubmed: 12874198doi: 10.4049/jimmunol.171.3.1133google scholar: lookup
                    35. Molinari P, García-Nuñez S, Gravisaco MJ, Carrillo E, Berinstein A, Taboga O. Baculovirus treatment fully protects mice against a lethal challenge of FMDV.. Antiviral Res 2010 Aug;87(2):276-9.
                      pubmed: 20580746doi: 10.1016/j.antiviral.2010.05.008google scholar: lookup
                    36. Hartman ZC, Black EP, Amalfitano A. Adenoviral infection induces a multi-faceted innate cellular immune response that is mediated by the toll-like receptor pathway in A549 cells.. Virology 2007 Feb 20;358(2):357-72.
                      pubmed: 17027060doi: 10.1016/j.virol.2006.08.041google scholar: lookup
                    37. Muruve DA. The innate immune response to adenovirus vectors.. Hum Gene Ther 2004 Dec;15(12):1157-66.
                      pubmed: 15684693doi: 10.1089/hum.2004.15.1157google scholar: lookup
                    38. Muruve DA, Barnes MJ, Stillman IE, Libermann TA. Adenoviral gene therapy leads to rapid induction of multiple chemokines and acute neutrophil-dependent hepatic injury in vivo.. Hum Gene Ther 1999 Apr 10;10(6):965-76.
                      pubmed: 10223730doi: 10.1089/10430349950018364google scholar: lookup
                    39. Zhang Y, Chirmule N, Gao GP, Qian R, Croyle M, Joshi B, Tazelaar J, Wilson JM. Acute cytokine response to systemic adenoviral vectors in mice is mediated by dendritic cells and macrophages.. Mol Ther 2001 May;3(5 Pt 1):697-707.
                      pubmed: 11356075doi: 10.1006/mthe.2001.0329google scholar: lookup
                    40. Marié I, Durbin JE, Levy DE. Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7.. EMBO J 1998 Nov 16;17(22):6660-9.
                      pmc: PMC1171011pubmed: 9822609doi: 10.1093/emboj/17.22.6660google scholar: lookup
                    41. Taub DD, Sayers TJ, Carter CR, Ortaldo JR. Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis.. J Immunol 1995 Oct 15;155(8):3877-88.
                      pubmed: 7561094

                    Citations

                    This article has been cited 12 times.
                    1. Scaglione A, Opp S, Hurtado A, Lin Z, Pampeno C, Noval MG, Thannickal SA, Stapleford KA, Meruelo D. Combination of a Sindbis-SARS-CoV-2 Spike Vaccine and αOX40 Antibody Elicits Protective Immunity Against SARS-CoV-2 Induced Disease and Potentiates Long-Term SARS-CoV-2-Specific Humoral and T-Cell Immunity.. Front Immunol 2021;12:719077.
                      doi: 10.3389/fimmu.2021.719077pubmed: 34394127google scholar: lookup
                    2. Diaz-San Segundo F, Medina GN, Azzinaro P, Gutkoska J, Mogulothu A, Attreed SE, Lombardi KR, Shields J, Hudock TA, de Los Santos T. Use of Protein Pegylation to Prolong the Antiviral Effect of IFN Against FMDV.. Front Microbiol 2021;12:668890.
                      doi: 10.3389/fmicb.2021.668890pubmed: 34025625google scholar: lookup
                    3. Diaz-San Segundo F, Medina GN, Spinard E, Kloc A, Ramirez-Medina E, Azzinaro P, Mueller S, Rieder E, de Los Santos T. Use of Synonymous Deoptimization to Derive Modified Live Attenuated Strains of Foot and Mouth Disease Virus.. Front Microbiol 2020;11:610286.
                      doi: 10.3389/fmicb.2020.610286pubmed: 33552021google scholar: lookup
                    4. Medina GN, de Los Santos T, Diaz-San Segundo F. Use of IFN-Based Biotherapeutics to Harness the Host Against Foot-And-Mouth Disease.. Front Vet Sci 2020;7:465.
                      doi: 10.3389/fvets.2020.00465pubmed: 32851039google scholar: lookup
                    5. Medina GN, Azzinaro P, Ramirez-Medina E, Gutkoska J, Fang Y, Diaz-San Segundo F, de Los Santos T. Impairment of the DeISGylation Activity of Foot-and-Mouth Disease Virus Lpro Causes Attenuation In Vitro and In Vivo.. J Virol 2020 Jun 16;94(13).
                      doi: 10.1128/JVI.00341-20pubmed: 32295921google scholar: lookup
                    6. Rai DK, Diaz-San Segundo F, Campagnola G, Keith A, Schafer EA, Kloc A, de Los Santos T, Peersen O, Rieder E. Attenuation of Foot-and-Mouth Disease Virus by Engineered Viral Polymerase Fidelity.. J Virol 2017 Aug 1;91(15).
                      doi: 10.1128/JVI.00081-17pubmed: 28515297google scholar: lookup
                    7. Ramírez-Carvajal L, Diaz-San Segundo F, Ramirez-Medina E, Rodríguez LL, de Los Santos T. Constitutively Active IRF7/IRF3 Fusion Protein Completely Protects Swine against Foot-and-Mouth Disease.. J Virol 2016 Oct 1;90(19):8809-21.
                      doi: 10.1128/JVI.00800-16pubmed: 27466421google scholar: lookup
                    8. Stenfeldt C, Diaz-San Segundo F, de Los Santos T, Rodriguez LL, Arzt J. The Pathogenesis of Foot-and-Mouth Disease in Pigs.. Front Vet Sci 2016;3:41.
                      doi: 10.3389/fvets.2016.00041pubmed: 27243028google scholar: lookup
                    9. Mamber SW, Lins J, Gurel V, Hutcheson DP, Pinedo P, Bechtol D, Krakowka S, Fields-Henderson R, Cummins JM. Low-dose oral interferon modulates expression of inflammatory and autoimmune genes in cattle.. Vet Immunol Immunopathol 2016 Apr;172:64-71.
                      doi: 10.1016/j.vetimm.2016.03.006pubmed: 27032505google scholar: lookup
                    10. Diaz-San Segundo F, Medina GN, Ramirez-Medina E, Velazquez-Salinas L, Koster M, Grubman MJ, de los Santos T. Synonymous Deoptimization of Foot-and-Mouth Disease Virus Causes Attenuation In Vivo while Inducing a Strong Neutralizing Antibody Response.. J Virol 2016 Feb 1;90(3):1298-310.
                      doi: 10.1128/JVI.02167-15pubmed: 26581977google scholar: lookup
                    11. Ramírez-Carvajal L, Díaz-San Segundo F, Hickman D, Long CR, Zhu J, Rodríguez LL, de los Santos T. Expression of porcine fusion protein IRF7/3(5D) efficiently controls foot-and-mouth disease virus replication.. J Virol 2014 Oct;88(19):11140-53.
                      doi: 10.1128/JVI.00372-14pubmed: 25031341google scholar: lookup
                    12. Habiela M, Seago J, Perez-Martin E, Waters R, Windsor M, Salguero FJ, Wood J, Charleston B, Juleff N. Laboratory animal models to study foot-and-mouth disease: a review with emphasis on natural and vaccine-induced immunity.. J Gen Virol 2014 Nov;95(Pt 11):2329-2345.
                      doi: 10.1099/vir.0.068270-0pubmed: 25000962google scholar: lookup
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