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Herpesviral vectors and their application in oncolytic therapy, vaccination, and gene transfer

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Abstract

Herpesviruses are enveloped DNA viruses that infect vertebrate cells. Their high potential cloning capacity and the lifelong persistence of their genomes in various host cells make them attractive platforms for vector-based therapy. In this review, we would like to highlight recent advances of three major areas of herpesvirus vector development and application: (i) oncolytic therapy, (ii) recombinant vaccines, and (iii) large capacity gene transfer vehicles.

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References

  1. A.J. Davison, Overview of classification. In Human Herpesviruses: Biology, Therapy and Immunoprophylaxis, ed. by A. Arvin, G. Campadelli-Fiume, E. Mocarski, P. S. Moore, B. Roizman, R. Whitley, et al. (Cambridge University Press; 2007)

  2. C.E. Thomas, A. Ehrhardt, M.A. Kay, Progress and problems with the use of viral vectors for gene therapy. Nat. Rev. Genet. 4(5), 346–358 (2003). doi:10.1038/nrg1066.

    Article  CAS  PubMed  Google Scholar 

  3. B.L. Liu, M. Robinson, Z.Q. Han, R.H. Branston, C. English, P. Reay et al., ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther. 10(4), 292–303 (2003). doi:10.1038/sj.gt.3301885.

    Article  CAS  PubMed  Google Scholar 

  4. R.H. Andtbacka, H.L. Kaufman, F. Collichio, T. Amatruda, N. Senzer, J. Chesney et al., Talimogene laherparepvec improves durable response rate in patients with advanced melanoma. J. Clin. Oncol. 33(25), 2780–2788 (2015). doi:10.1200/JCO.2014.58.3377.

    Article  CAS  PubMed  Google Scholar 

  5. S.G. Hansen, M. Piatak Jr., A.B. Ventura, C.M. Hughes, R.M. Gilbride, J.C. Ford et al., Immune clearance of highly pathogenic SIV infection. Nature 502(7469), 100–104 (2013). doi:10.1038/nature12519.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. D. Jerusalinsky, M.V. Baez, A.L. Epstein, Herpes simplex virus type 1-based amplicon vectors for fundamental research in neurosciences and gene therapy of neurological diseases. J. Physiol. Paris 106(1–2), 2–11 (2012). doi:10.1016/j.jphysparis.2011.11.003.

    Article  PubMed  Google Scholar 

  7. E.S. Mocarski, L.E. Post, B. Roizman, Molecular engineering of the herpes simplex virus genome: insertion of a second L-S junction into the genome causes additional genome inversions. Cell 22(1 Pt 1), 243–255 (1980).

    Article  CAS  PubMed  Google Scholar 

  8. J.R. Smiley, Construction in vitro and rescue of a thymidine kinase-deficient deletion mutation of herpes simplex virus. Nature 285(5763), 333–335 (1980).

    Article  CAS  PubMed  Google Scholar 

  9. R.R. Spaete, E.S. Mocarski, Insertion and deletion mutagenesis of the human cytomegalovirus genome. Proc. Nat. Acad. Sci. USA 84(20), 7213–7217 (1987)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. W.C. Manning, E.S. Mocarski, Insertional mutagenesis of the murine cytomegalovirus genome: one prominent alpha gene (ie2) is dispensable for growth. Virology 167(2), 477–484 (1988)

    CAS  PubMed  Google Scholar 

  11. H. Shizuya, B. Birren, U.J. Kim, V. Mancino, T. Slepak, Y. Tachiiri et al., Cloning and stable maintenance of 300-kilobase-pair fragments of human DNA in Escherichia coli using an F-factor-based vector. Proc. Nat. Acad. Sci. USA 89(18), 8794–8797 (1992)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Q. Tao, H.B. Zhang, Cloning and stable maintenance of DNA fragments over 300 kb in Escherichia coli with conventional plasmid-based vectors. Nucl. Acids Res. 26(21), 4901–4909 (1998)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. G.A. Smith, L.W. Enquist, Construction and transposon mutagenesis in Escherichia coli of a full-length infectious clone of pseudorabies virus, an alphaherpesvirus. J. Virol 73(8), 6405–6414 (1999)

    CAS  PubMed  PubMed Central  Google Scholar 

  14. M. Messerle, I. Crnkovic, W. Hammerschmidt, H. Ziegler, U.H. Koszinowski, Cloning and mutagenesis of a herpesvirus genome as an infectious bacterial artificial chromosome. Proc. Nat. Acad. Sci. USA 94(26), 14759–14763 (1997)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. W. Brune, M. Messerle, U.H. Koszinowski, Forward with BACs: new tools for herpesvirus genomics. Trends Genet. 16(6), 254–259 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Z. Ruzsics, U.H. Koszinowski, Mutagenesis of the cytomegalovirus genome. Curr. Top. Microbiol. Immunol. 325, 41–61 (2008).

    CAS  PubMed  Google Scholar 

  17. K. Narayanan, Q. Chen, Bacterial artificial chromosome mutagenesis using recombineering. J. Biomed. Biotechnol. 2011, 971296 (2011). doi:10.1155/2011/971296.

    Article  PubMed  Google Scholar 

  18. B.K. Tischer, G.A. Smith, N. Osterrieder, En passant mutagenesis: a two step markerless red recombination system. Methods Mol. Biol. 634, 421–430 (2010). doi:10.1007/978-1-60761-652-8_30.

    Article  CAS  PubMed  Google Scholar 

  19. A. Arvin, G. Campadelli-Fiume, E. Mocarski, P.S. Moore, B. Roizman, et al. (eds.), Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis (Cambridge University Press, Cambridge, 2007)

    Google Scholar 

  20. G.B. Elion, The biochemistry and mechanism of action of acyclovir. J Antimicrob Chemother 12(Suppl B), 9–17 (1983)

    Article  CAS  PubMed  Google Scholar 

  21. G. Campadelli-Fiume, B. Petrovic, V. Leoni, T. Gianni, E. Avitabile, C. Casiraghi et al., Retargeting strategies for oncolytic herpes simplex viruses. Viruses. 8(3), 63 (2016). doi:10.3390/v8030063.

    Article  PubMed  PubMed Central  Google Scholar 

  22. M. Nygardas, H. Paavilainen, N. Muther, C.H. Nagel, M. Roytta, B. Sodeik et al., A herpes simplex virus-derived replicative vector expressing LIF limits experimental demyelinating disease and modulates autoimmunity. PLoS ONE 8(5), e64200 (2013). doi:10.1371/journal.pone.0064200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. C.H. Nagel, A. Pohlmann, B. Sodeik, Construction and characterization of bacterial artificial chromosomes (BACs) containing herpes simplex virus full-length genomes. Methods Mol. Biol. 1144, 43–62 (2014). doi:10.1007/978-1-4939-0428-0_4.

    Article  PubMed  Google Scholar 

  24. C. Funk, M. Ott, V. Raschbichler, C.H. Nagel, A. Binz, B. Sodeik et al., The herpes simplex virus protein pUL31 escorts nucleocapsids to sites of nuclear egress, a process coordinated by its N-terminal domain. PLoS Pathog. 11(6), e1004957 (2015). doi:10.1371/journal.ppat.1004957.

    Article  PubMed  PubMed Central  Google Scholar 

  25. G. Ungerechts, S. Bossow, B. Leuchs, P.S. Holm, J. Rommelaere, M. Coffey et al., Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses. Mol. Ther. Methods Clin. Dev. 3, 16018 (2016). doi:10.1038/mtm.2016.18.

    Article  PubMed  PubMed Central  Google Scholar 

  26. N.A. Sokolowski, H. Rizos, R.J. Diefenbach, Oncolytic virotherapy using herpes simplex virus: how far have we come? Oncol. Virother. 4, 207–219 (2015). doi:10.2147/OV.S66086.

    Google Scholar 

  27. P.R. Buijs, J.H. Verhagen, C.H. van Eijck, B.G. van den Hoogen, Oncolytic viruses: from bench to bedside with a focus on safety. Hum. Vaccin. Immunother. 11(7), 1573–1584 (2015). doi:10.1080/21645515.2015.1037058.

    Article  PubMed  PubMed Central  Google Scholar 

  28. D.R. Wilcox, R. Longnecker, The herpes simplex virus neurovirulence factor gamma34.5: revealing virus-host interactions. PLoS Pathog. 12(3), e1005449 (2016). doi:10.1371/journal.ppat.1005449.

    Article  PubMed  PubMed Central  Google Scholar 

  29. C. Krummenacher, A. Carfi, R.J. Eisenberg, G.H. Cohen, Entry of herpesviruses into cells: the enigma variations. Adv. Exp. Med. Biol. 790, 178–195 (2013). doi:10.1007/978-1-4614-7651-1_10.

    Article  CAS  PubMed  Google Scholar 

  30. E.E. Heldwein, gH/gL supercomplexes at early stages of herpesvirus entry. Curr. Opin. Virol. 18, 1–8 (2016). doi:10.1016/j.coviro.2016.01.010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. V. Gatta, B. Petrovic, G. Campadelli-Fiume, The engineering of a novel ligand in gH confers to HSV an expanded tropism independent of gD activation by its receptors. PLoS Pathog. 11(5), e1004907 (2015). doi:10.1371/journal.ppat.1004907.

    Article  PubMed  PubMed Central  Google Scholar 

  32. B. Petrovic, T. Gianni, V. Gatta, G. Campadelli-Fiume, Insertion of a ligand to HER2 in gB retargets HSV tropism and obviates the need for activation of the other entry glycoproteins. PLoS Pathog. 13(4), e1006352 (2017). doi:10.1371/journal.ppat.1006352.

    Article  PubMed  PubMed Central  Google Scholar 

  33. C.A. Alvarez-Breckenridge, B.D. Choi, C.M. Suryadevara, E.A. Chiocca, Potentiating oncolytic viral therapy through an understanding of the initial immune responses to oncolytic viral infection. Curr Opin Virol. 13, 25–32 (2015). doi:10.1016/j.coviro.2015.03.015.

    Article  CAS  PubMed  Google Scholar 

  34. A. Melcher, K. Parato, C.M. Rooney, J.C. Bell, Thunder and lightning: immunotherapy and oncolytic viruses collide. Mol. Ther. 19(6), 1008–1016 (2011). doi:10.1038/mt.2011.65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. A. Pourchet, S.R. Fuhrmann, K.A. Pilones, S. Demaria, A.B. Frey, M. Mulvey et al., CD8(+) T-cell immune evasion enables oncolytic virus immunotherapy. EBioMedicine. 5, 59–67 (2016). doi:10.1016/j.ebiom.2016.01.022

    Article  PubMed  PubMed Central  Google Scholar 

  36. B.D. Lichty, C.J. Breitbach, D.F. Stojdl, J.C. Bell, Going viral with cancer immunotherapy. Nat. Rev. Cancer 14(8), 559–567 (2014). doi:10.1038/nrc3770.

    Article  CAS  PubMed  Google Scholar 

  37. R.S. Coffin, From virotherapy to oncolytic immunotherapy: where are we now? Curr. Opin. Virol. 13, 93–100 (2015). doi:10.1016/j.coviro.2015.06.005.

    Article  CAS  PubMed  Google Scholar 

  38. R.H. Andtbacka, M. Ross, I. Puzanov, M. Milhem, F. Collichio, K.A. Delman et al., Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in patients with melanoma treated in the OPTiM phase III clinical trial. Ann. Surg. Oncol. 23(13), 4169–4177 (2016). doi:10.1245/s10434-016-5286-0.

    Article  PubMed  PubMed Central  Google Scholar 

  39. D.M. Pardoll, The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 12(4), 252–264 (2012). doi:10.1038/nrc3239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. I. Puzanov, M.M. Milhem, D. Minor, O. Hamid, A. Li, L. Chen et al., Talimogene laherparepvec in combination with ipilimumab in previously untreated, unresectable stage IIIB-IV melanoma. J. Clin. Oncol. 34(22), 2619–2626 (2016). doi:10.1200/JCO.2016.67.1529.

    Article  CAS  PubMed  Google Scholar 

  41. S.J. Russell, K.W. Peng, J.C. Bell, Oncolytic virotherapy. Nat. Biotechnol. 30(7), 658–670 (2012). doi:10.1038/nbt.2287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. K.J. Allan, D.F. Stojdl, S.L. Swift, High-throughput screening to enhance oncolytic virus immunotherapy. Oncolytic Virother. 5, 15–25 (2016). doi:10.2147/OV.S66217.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. B. Dong, D.S. Zarlenga, X. Ren, An overview of live attenuated recombinant pseudorabies viruses for use as novel vaccines. J. Immunol. Res. 2014, 824630 (2014). doi:10.1155/2014/824630.

    Article  PubMed  PubMed Central  Google Scholar 

  44. P. Marconi, R. Argnani, A.L. Epstein, R. Manservigi, HSV as a vector in vaccine development and gene therapy. Adv. Exp. Med. Biol. 655, 118–144 (2009). doi:10.1007/978-1-4419-1132-2_10.

    Article  CAS  PubMed  Google Scholar 

  45. D. Watanabe, Medical application of herpes simplex virus. J. Dermatol. Sci. 57(2), 75–82 (2010). doi:10.1016/j.jdermsci.2009.10.014.

    Article  CAS  PubMed  Google Scholar 

  46. U. Karrer, M. Wagner, S. Sierro, A. Oxenius, H. Hengel, T. Dumrese et al., Expansion of protective CD8+ T-cell responses driven by recombinant cytomegaloviruses. J. Virol. 78(5), 2255–2264 (2004)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. B. Bolinger, S. Sims, G. O’Hara, C. de Lara, E. Tchilian, S. Firner et al., A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector. J. Immunol. 190(8), 4162–4174 (2013). doi:10.4049/jimmunol.1202665.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. G.A. O’Hara, S.P. Welten, P. Klenerman, R. Arens, Memory T cell inflation: understanding cause and effect. Trends Immunol. 33(2), 84–90 (2012). doi:10.1016/j.it.2011.11.005.

    Article  PubMed  Google Scholar 

  49. S.G. Hansen, H.L. Wu, B.J. Burwitz, C.M. Hughes, K.B. Hammond, A.B. Ventura et al., Broadly targeted CD8(+) T cell responses restricted by major histocompatibility complex E. Science 351(6274), 714–720 (2016). doi:10.1126/science.aac9475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. B.J. Burwitz, D. Malouli, B.N. Bimber, J.S. Reed, A.B. Ventura, M.H. Hancock et al., Cross-species rhesus cytomegalovirus infection of cynomolgus macaques. PLoS Pathog. 12(11), e1006014 (2016). doi:10.1371/journal.ppat.1006014.

    Article  PubMed  PubMed Central  Google Scholar 

  51. E.S. Barton, D.W. White, J.S. Cathelyn, K.A. Brett-McClellan, M. Engle, M.S. Diamond et al., Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447(7142), 326–329 (2007). doi:10.1038/nature05762.

    Article  CAS  PubMed  Google Scholar 

  52. P.C. Beverley, Z. Ruzsics, A. Hey, C. Hutchings, S. Boos, B. Bolinger et al., A novel murine cytomegalovirus vaccine vector protects against Mycobacterium tuberculosis. J Immunol. 193(5), 2306–2316 (2014). doi:10.4049/jimmunol.1302523.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. I. Brizic, T. Lenac Rovis, A. Krmpotic, S. Jonjic, MCMV avoidance of recognition and control by NK cells. Semin Immunopathol. 36(6), 641–650 (2014). doi:10.1007/s00281-014-0441-9.

    Article  CAS  PubMed  Google Scholar 

  54. A. Moosmann, N. Khan, M. Cobbold, C. Zentz, H.J. Delecluse, G. Hollweck et al., B cells immortalized by a mini-Epstein-Barr virus encoding a foreign antigen efficiently reactivate specific cytotoxic T cells. Blood 100(5), 1755–1764 (2002).

    CAS  PubMed  Google Scholar 

  55. S. Ameres, X. Liang, M. Wiesner, J. Mautner, A. Moosmann, A diverse repertoire of CD4 T cells targets the immediate-early 1 protein of human cytomegalovirus. Front. Immunol. 6, 598 (2015). doi:10.3389/fimmu.2015.00598.

    Article  PubMed  PubMed Central  Google Scholar 

  56. M. Wiesner, C. Zentz, M.H. Hammer, M. Cobbold, F. Kern, H.J. Kolb et al., Selection of CMV-specific CD8+ and CD4+ T cells by mini-EBV-transformed B cell lines. Eur. J. Immunol. 35(7), 2110–2121 (2005). doi:10.1002/eji.200425936.

    Article  CAS  PubMed  Google Scholar 

  57. E. Hettich, A. Janz, R. Zeidler, D. Pich, E. Hellebrand, B. Weissflog et al., Genetic design of an optimized packaging cell line for gene vectors transducing human B cells. Gene Ther. 13(10), 844–856 (2006). doi:10.1038/sj.gt.3302714.

    CAS  PubMed  Google Scholar 

  58. A. Gimenez-Cassina, R. Wade-Martins, S. Gomez-Sebastian, J.C. Corona, F. Lim, J. Diaz-Nido, Infectious delivery and long-term persistence of transgene expression in the brain by a 135-kb iBAC-FXN genomic DNA expression vector. Gene Ther. 18(10), 1015–1019 (2011). doi:10.1038/gt.2011.45.

    Article  CAS  PubMed  Google Scholar 

  59. M.M. Lufino, P.A. Edser, M.A. Quail, S. Rice, D.J. Adams, R. Wade-Martins, The infectious BAC genomic DNA expression library: a high capacity vector system for functional genomics. Sci. Rep. 6, 28644 (2016). doi:10.1038/srep28644.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. A.F. Meier, M. Suter, E.M. Schraner, B.M. Humbel, K. Tobler, M. Ackermann et al., Transfer of anti-rotavirus antibodies during pregnancy and in milk following maternal vaccination with a herpes simplex virus type-1 amplicon vector. Int. J. Mol. Sci. (2017). doi:10.3390/ijms18020431

    PubMed  PubMed Central  Google Scholar 

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Funding

This study was funded by the Deutsches Zentrum für Infektionsforschung (DZIF TTU-IICH-708.2 to A.R. and Z.R).

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Authors and Affiliations

  1. Institute for Interfacial Engineering and Plasma Technology IGVP, University of Stuttgart, Nobelstrasse 12, 70569, Stuttgart, Germany

    Susanne M. Bailer & Christina Funk

  2. Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB, Nobelstrasse 12, 70569, Stuttgart, Germany

    Susanne M. Bailer & Christina Funk

  3. Department for Medical Microbiology and Hygiene, Institute of Virology, University Medical Center Freiburg, Hermann-Herder-Strasse 11, 79104, Freiburg, Germany

    André Riedl & Zsolt Ruzsics

  4. German Center for Infection Research - DZIF, Freiburg, Germany

    André Riedl & Zsolt Ruzsics

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  1. Susanne M. Bailer
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  2. Christina Funk
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  3. André Riedl
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  4. Zsolt Ruzsics
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Correspondence to Susanne M. Bailer or Zsolt Ruzsics.

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Bailer, S.M., Funk, C., Riedl, A. et al. Herpesviral vectors and their application in oncolytic therapy, vaccination, and gene transfer. Virus Genes 53, 741–748 (2017). https://doi.org/10.1007/s11262-017-1482-7

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