Virologica Sinica

, Volume 27, Issue 2, pp 71–82 | Cite as

Genetic modification of baculovirus expression vectors

Article

Abstract

As a protein expression vector, the baculovirus demonstrates many advantages over other vectors. With the development of biotechnology, baculoviral vectors have been genetically modified to facilitate high level expression of heterologous proteins in both insect and mammalian cells. These modifications include utilization of different promoters and signal peptides, deletion or replacement of viral genes for increasing protein secretion, integration of polycistronic expression cassette for producing protein complexes, and baculovirus pseudotyping, promoter accommodation or surface display for enhancing mammalian cell targeting gene delivery. This review summarizes the development and the current state of art of the baculovirus expression system. Further development of baculovirus expression systems will make them even more feasible and accessible for advanced applications.

Key words

Baculovirus Protein expression Promoters Signal peptides Gene delivery 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Airenne K J, Hiltunen M O, Turunen M P, et al. 2000. Baculovirus-mediated periadventitial gene transfer to rabbit carotid artery. Gene Ther, 7:1499–1504.PubMedCrossRefGoogle Scholar
  2. 2.
    Allet B, Bernard A R, Hochmann A, et al. 1997. A bacterial signal peptide directs efficient secretion of eukaryotic proteins in the baculovirus expression system. Protein Expr Purif, 9:61–68.PubMedCrossRefGoogle Scholar
  3. 3.
    Altmann F, Staudacher E, Wilson I B, et al. 1999. Insect cells as hosts for the expression of recombinant glycoproteins. Glycoconj J, 16:109–123.PubMedCrossRefGoogle Scholar
  4. 4.
    Ayres M D, Howard S C, Kuzio J, et al. 1994. The complete DNA sequence of Autographa californica nuclear polyhedrosis virus. Virology, 202:586–605.PubMedCrossRefGoogle Scholar
  5. 5.
    Barsoum J, Brown R, McKee M, et al. 1997. Efficient transduction of mammalian cells by a recombinant baculovirus having the vesicular stomatitis virus G glycoprotein. Hum Gene Ther, 8:2011–2018.PubMedCrossRefGoogle Scholar
  6. 6.
    Berger I, Fitzgerald D J, Richmond T J. 2004. Baculovirus expression system for heterologous multiprotein complexes. Nat Biotechnol, 22:1583–1587.PubMedCrossRefGoogle Scholar
  7. 7.
    Bertolotti-Ciarlet A, Ciarlet M, Crawford S E, et al. 2003. Immunogenicity and protective efficacy of rotavirus 2/6-virus-like particles produced by a dual baculovirus expression vector and administered intramuscularly, intranasally, or orally to mice. Vaccine, 21:3885–3900.PubMedCrossRefGoogle Scholar
  8. 8.
    Boublik Y, Di Bonito P, Jones I M. 1995. Eukaryotic virus display: engineering the major surface glycoprotein of the Autographa californica nuclear polyhedrosis virus (AcNPV) for the presentation of foreign proteins on the virus surface. Biotechnology (N Y), 13:1079–1084.CrossRefGoogle Scholar
  9. 9.
    Boyce F M, Bucher N L. 1996. Baculovirus-mediated gene transfer into mammalian cells. Proc Natl Acad Sci U S A, 93:2348–2352.PubMedCrossRefGoogle Scholar
  10. 10.
    Bright R A, Carter D M, Daniluk S, et al. 2007. Influenza virus-like particles elicit broader immune responses than whole virion inactivated influenza virus or recombinant hemagglutinin. Vaccine, 25:3871–3878.PubMedCrossRefGoogle Scholar
  11. 11.
    Carbonell L F, Klowden M J, Miller L K. 1985. Baculovirus-mediated expression of bacterial genes in dipteran and mammalian cells. J Virol, 56:153–160.PubMedGoogle Scholar
  12. 12.
    Carbonell L F, Miller L K. 1987. Baculovirus interaction with nontarget organisms: a virus-borne reporter gene is not expressed in two mammalian cell lines. Appl Environ Microbiol, 53:1412–1417.PubMedGoogle Scholar
  13. 13.
    Chen Y, Yao B, Zhu Z, et al. 2004. A constitutive super-enhancer: homologous region 3 of Bombyx mori nucleopolyhedrovirus. Biochem Biophys Res Commun, 318:1039–1044.PubMedCrossRefGoogle Scholar
  14. 14.
    Chen Y J, Chen W S, Wu T Y. 2005. Development of a bi-cistronic baculovirus expression vector by the Rhopalosiphum padi virus 5′ internal ribosome entry site. Biochem Biophys Res Commun, 335:616–623.PubMedCrossRefGoogle Scholar
  15. 15.
    Cheshenko N, Krougliak N, Eisensmith R C, et al. 2001. A novel system for the production of fully deleted adenovirus vectors that does not require helper adenovirus. Gene Ther, 8:846–854.PubMedCrossRefGoogle Scholar
  16. 16.
    Condreay J P, Witherspoon S M, Clay W C, et al. 1999. Transient and stable gene expression in mammalian cells transduced with a recombinant baculovirus vector. Proc Natl Acad Sci U S A, 96:127–132.PubMedCrossRefGoogle Scholar
  17. 17.
    Ernst W, Schinko T, Spenger A, et al. 2006. Improving baculovirus transduction of mammalian cells by surface display of a RGD-motif. J Biotechnol, 126:237–240.PubMedCrossRefGoogle Scholar
  18. 18.
    Fang M, Dai X, Theilmann D A. 2007. Autographa californica multiple nucleopolyhedrovirus EXON0 (ORF141) is required for efficient egress of nucleocapsids from the nucleus. J Virol, 81:9859–9869.PubMedCrossRefGoogle Scholar
  19. 19.
    Furlong A M, Thomsen D R, Marotti K R, et al. 1988. Active human tissue plasminogen activator secreted from insect cells using a baculovirus vector. Biotechnol Appl Biochem, 10:454–464.PubMedGoogle Scholar
  20. 20.
    Futatsumori-Sugai M, Tsumoto K. 2010. Signal peptide design for improving recombinant protein secretion in the baculovirus expression vector system. Biochem Biophys Res Commun, 391:931–935.PubMedCrossRefGoogle Scholar
  21. 21.
    Gao H, Wang Y, Li N, et al. 2007. Efficient gene delivery into mammalian cells mediated by a recombinant baculovirus containing a whispovirus ie1 promoter, a novel shuttle promoter between insect cells and mammalian cells. J Biotechnol, 131:138–143.PubMedCrossRefGoogle Scholar
  22. 22.
    Ge J, Huang Y, Hu X, et al. 2007. A surface-modified baculovirus vector with improved gene delivery to B-lymphocytic cells. J Biotechnol, 129:367–372.PubMedCrossRefGoogle Scholar
  23. 23.
    Ghosh S, Parvez M K, Banerjee K, et al. 2002. Baculovirus as mammalian cell expression vector for gene therapy: an emerging strategy. Mol Ther, 6:5–11.PubMedCrossRefGoogle Scholar
  24. 24.
    Gomi S, Majima K, Maeda S. 1999. Sequence analysis of the genome of Bombyx mori nucleopolyhedrovirus. J Gen Virol, 80(Pt 5):1323–1337.PubMedGoogle Scholar
  25. 25.
    Granados R R, Federici B A. 1986. The biology of baculoviruses. Boca Raton: CRC Press.Google Scholar
  26. 26.
    Groner A, Granados R R, Burand J P. 1984. Interaction of Autographa californica nuclear polyhedrosis virus with two nonpermissive cell lines. Intervirology, 21:203–209.PubMedCrossRefGoogle Scholar
  27. 27.
    Gronowski A M, Hilbert D M, Sheehan K C, et al. 1999. Baculovirus stimulates antiviral effects in mammalian cells. J Virol, 73:9944–9951.PubMedGoogle Scholar
  28. 28.
    Harrison R L, Summers M D. 1995. Mutations in the Autographa californica multinucleocapsid nuclear polyhedrosis virus 25 kDa protein gene result in reduced virion occlusion, altered intranuclear envelopment and enhanced virus production. J Gen Virol, 76(Pt 6):1451–1459.PubMedCrossRefGoogle Scholar
  29. 29.
    Hill-Perkins M S, Possee R D. 1990. A baculovirus expression vector derived from the basic protein promoter of Autographa californica nuclear polyhedrosis virus. J Gen Virol, 71( Pt 4):971–976.PubMedCrossRefGoogle Scholar
  30. 30.
    Hitchman R B, Possee R D, Crombie A T, et al. 2010. Genetic modification of a baculovirus vector for increased expression in insect cells. Cell Biol Toxicol, 26:57–68.PubMedCrossRefGoogle Scholar
  31. 31.
    Hitchman R B, Possee R D, Siaterli E, et al. 2010. Improved expression of secreted and membrane-targeted proteins in insect cells. Biotechnol Appl Biochem, 56:85–93.PubMedCrossRefGoogle Scholar
  32. 32.
    Hiyoshi M, Kageshima A, Kato T, et al. 2007. Construction of a cysteine protease deficient Bombyx mori multiple nucleopolyhedrovirus bacmid and its application to improve expression of a fusion protein. J Virol Methods, 144:91–97.PubMedCrossRefGoogle Scholar
  33. 33.
    Hofmann C, Sandig V, Jennings G, et al. 1995. Efficient gene transfer into human hepatocytes by baculovirus vectors. Proc Natl Acad Sci U S A, 92:10099–10103.PubMedCrossRefGoogle Scholar
  34. 34.
    Hu Y C, Lin S Y, Chen G Y. 2011. Recent Patents on the Baculovirus Systems. Recent Pat Biotechnol. (Epub ahead of print)Google Scholar
  35. 35.
    Huser A, Rudolph M, Hofmann C. 2001. Incorporation of decay-accelerating factor into the baculovirus envelope generates complement-resistant gene transfer vectors. Nat Biotechnol, 19:451–455.PubMedCrossRefGoogle Scholar
  36. 36.
    Ishiyama S, Ikeda M. 2010. High-level expression and improved folding of proteins by using the vp39 late promoter enhanced with homologous DNA regions. Biotechnol Lett, 32:1637–1647.PubMedCrossRefGoogle Scholar
  37. 37.
    Jarvis D L, Finn E E. 1996. Modifying the insect cell N-glycosylation pathway with immediate early baculovirus expression vectors. Nat Biotechnol, 14:1288–1292.PubMedCrossRefGoogle Scholar
  38. 38.
    Jarvis D L, Fleming J A, Kovacs G R, et al. 1990. Use of early baculovirus promoters for continuous expression and efficient processing of foreign gene products in stably transformed lepidopteran cells. Biotechnology (N Y), 8:950–955.CrossRefGoogle Scholar
  39. 39.
    Jarvis D L, Summers M D. 1989. Glycosylation and secretion of human tissue plasminogen activator in recombinant baculovirus-infected insect cells. Mol Cell Biol, 9:214–223.PubMedGoogle Scholar
  40. 40.
    Jarvis D L, Summers M D, Garcia A, et al. 1993. Influence of different signal peptides and prosequences on expression and secretion of human tissue plasminogen activator in the baculovirus system. J Biol Chem, 268:16754–16762.PubMedGoogle Scholar
  41. 41.
    Kaba S A, Salcedo A M, Wafula P O, et al. 2004. Development of a chitinase and v-cathepsin negative bacmid for improved integrity of secreted recombinant proteins. J Virol Methods, 122:113–118.PubMedCrossRefGoogle Scholar
  42. 42.
    Kaikkonen M U, Raty J K, Airenne K J, et al. 2006. Truncated vesicular stomatitis virus G protein improves baculovirus transduction efficiency in vitro and in vivo. Gene Ther, 13:304–312.PubMedCrossRefGoogle Scholar
  43. 43.
    Keil G M, Klopfleisch C, Giesow K, et al. 2009. Novel vectors for simultaneous high-level dual protein expression in vertebrate and insect cells by recombinant baculoviruses. J Virol Methods, 160:132–137.PubMedCrossRefGoogle Scholar
  44. 44.
    King L A, Kaur K, Mann S G, et al. 1991. Secretion of single-chain urokinase-type plasminogen activator from insect cells. Gene, 106:151–157.PubMedCrossRefGoogle Scholar
  45. 45.
    Kost T A, Condreay J P. 1999. Recombinant baculoviruses as expression vectors for insect and mammalian cells. Curr Opin Biotechnol, 10:428–433.PubMedCrossRefGoogle Scholar
  46. 46.
    Kost T A, Condreay J P, Jarvis D L. 2005. Baculovirus as versatile vectors for protein expression in insect and mammalian cells. Nat Biotechnol, 23:567–575.PubMedCrossRefGoogle Scholar
  47. 47.
    Li Y, Yang Y, Wang S. 2005. Neuronal gene transfer by baculovirus-derived vectors accommodating a neurone-specific promoter. Exp Physiol, 90:39–44.PubMedCrossRefGoogle Scholar
  48. 48.
    Lo H R, Chou C C, Wu T Y, et al. 2002. Novel baculovirus DNA elements strongly stimulate activities of exogenous and endogenous promoters. J Biol Chem, 277:5256–5264.PubMedCrossRefGoogle Scholar
  49. 49.
    Luckow V A, Lee S C, Barry G F, et al. 1993. Efficient generation of infectious recombinant baculoviruses by site-specific transposon-mediated insertion of foreign genes into a baculovirus genome propagated in Escherichia coli. J Virol, 67:4566–4579.PubMedGoogle Scholar
  50. 50.
    Ma L, Tamarina N, Wang Y, et al. 2000. Baculovirus-mediated gene transfer into pancreatic islet cells. Diabetes, 49:1986–1991.PubMedCrossRefGoogle Scholar
  51. 51.
    Maeda S, Kawai T, Obinata M, et al. 1985. Production of human alpha-interferon in silkworm using a baculovirus vector. Nature, 315:592–594.PubMedCrossRefGoogle Scholar
  52. 52.
    Mahmood K, Bright R A, Mytle N, et al. 2008. H5N1 VLP vaccine induced protection in ferrets against lethal challenge with highly pathogenic H5N1 influenza viruses. Vaccine, 26:5393–5399.PubMedCrossRefGoogle Scholar
  53. 53.
    Matilainen H, Makela A R, Riikonen R, et al. 2006. RGD motifs on the surface of baculovirus enhance transduction of human lung carcinoma cells. J Biotechnol, 125:114–126.PubMedCrossRefGoogle Scholar
  54. 54.
    Meyer T H, van Endert P M, Uebel S, et al. 1994. Functional expression and purification of the ABC transporter complex associated with antigen processing (TAP) in insect cells. FEBS Lett, 351:443–447.PubMedCrossRefGoogle Scholar
  55. 55.
    Miller L K. 1993. Baculoviruses: high-level expression in insect cells. Curr Opin Genet Dev, 3:97–101.PubMedCrossRefGoogle Scholar
  56. 56.
    Mottershead D, van der Linden I, von Bonsdorff C H, et al. 1997. Baculoviral display of the green fluorescent protein and rubella virus envelope proteins. Biochem Biophys Res Commun, 238:717–722.PubMedCrossRefGoogle Scholar
  57. 57.
    Nakanishi T, Goto C, Kobayashi M, et al. 2010. Comparative studies of lepidopteran baculovirus-specific protein FP25K: development of a novel Bombyx mori nucleopolyhedrovirus-based vector with a modified fp25K gene. J Virol, 84:5191–5200.PubMedCrossRefGoogle Scholar
  58. 58.
    Noad R J, Stewart M, Boyce M, et al. 2009. Multigene expression of protein complexes by iterative modification of genomic Bacmid DNA. BMC Mol Biol, 10:87.PubMedCrossRefGoogle Scholar
  59. 59.
    Ojala K, Mottershead D G, Suokko A, et al. 2001. Specific binding of baculoviruses displaying gp64 fusion proteins to mammalian cells. Biochem Biophys Res Commun, 284:777–784.PubMedCrossRefGoogle Scholar
  60. 60.
    Olczak M, Olczak T. 2006. Comparison of different signal peptides for protein secretion in nonlytic insect cell system. Anal Biochem, 359:45–53.PubMedCrossRefGoogle Scholar
  61. 61.
    Pan Y, Zhao Q, Fang L, et al. 2009. Efficient gene delivery into mammalian cells by recombinant baculovirus containing a hybrid cytomegalovirus promoter/Semliki Forest virus replicon. J Gene Med, 11:1030–1038.PubMedCrossRefGoogle Scholar
  62. 62.
    Park E Y, Kageshima A, Kwon M S, et al. 2007. Enhanced production of secretory beta1, 3-N-acetylglucosaminyltransferase 2 fusion protein into hemolymph of Bombyx mori larvae using recombinant BmNPV bacmid integrated signal sequence. J Biotechnol, 129:681–688.PubMedCrossRefGoogle Scholar
  63. 63.
    Park S W, Lee H K, Kim T G, et al. 2001. Hepatocyte-specific gene expression by baculovirus pseudotyped with vesicular stomatitis virus envelope glycoprotein. Biochem Biophys Res Commun, 289:444–450.PubMedCrossRefGoogle Scholar
  64. 64.
    Pieroni L, Maione D, La Monica N. 2001. In vivo gene transfer in mouse skeletal muscle mediated by baculovirus vectors. Hum Gene Ther, 12:871–881.PubMedCrossRefGoogle Scholar
  65. 65.
    Possee R D, Thomas C J, King L A. 1999. The use of baculovirus vectors for the production of membrane proteins in insect cells. Biochem Soc Trans, 27:928–932.PubMedGoogle Scholar
  66. 66.
    Poul M A, Cerutti M, Chaabihi H, et al. 1995. Cassette baculovirus vectors for the production of chimeric, humanized, or human antibodies in insect cells. Eur J Immunol, 25:2005–2009.PubMedCrossRefGoogle Scholar
  67. 67.
    Rasmussen L, Battles J K, Ennis W H, et al. 1990. Characterization of virus-like particles produced by a recombinant baculovirus containing the gag gene of the bovine immunodeficiency-like virus. Virology, 178:435–451.PubMedCrossRefGoogle Scholar
  68. 68.
    Raty J K, Airenne K J, Marttila A T, et al. 2004. Enhanced gene delivery by avidin-displaying baculovirus. Mol Ther, 9:282–291.PubMedCrossRefGoogle Scholar
  69. 69.
    Rohrmann G F. 1992. Baculovirus structural proteins. J Gen Virol, 73( Pt 4):749–761.PubMedCrossRefGoogle Scholar
  70. 70.
    Sarkis C, Serguera C, Petres S, et al. 2000. Efficient transduction of neural cells in vitro and in vivo by a baculovirus-derived vector. Proc Natl Acad Sci U S A, 97:14638–14643.PubMedCrossRefGoogle Scholar
  71. 71.
    Shoji I, Aizaki H, Tani H, et al. 1997. Efficient gene transfer into various mammalian cells, including non-hepatic cells, by baculovirus vectors. J Gen Virol, 78( Pt 10):2657–2664.PubMedGoogle Scholar
  72. 72.
    Smith G E, Summers M D, Fraser M J. 1983. Production of human beta interferon in insect cells infected with a baculovirus expression vector. Mol Cell Biol, 3:2156–2165.PubMedGoogle Scholar
  73. 73.
    Suzuki T, Kanaya T, Okazaki H, et al. 1997. Efficient protein production using a Bombyx mori nuclear polyhedrosis virus lacking the cysteine proteinase gene. J Gen Virol, 78( Pt 12):3073–3080.PubMedGoogle Scholar
  74. 74.
    Tessier D C, Thomas D Y, Khouri H E, et al. 1991. Enhanced secretion from insect cells of a foreign protein fused to the honeybee melittin signal peptide. Gene, 98:177–183.PubMedCrossRefGoogle Scholar
  75. 75.
    Thiem S M, Miller L K. 1990. Differential gene expression mediated by late, very late and hybrid baculovirus promoters. Gene, 91:87–94.PubMedCrossRefGoogle Scholar
  76. 76.
    Thomas C J, Brown H L, Hawes C R, et al. 1998. Localization of a baculovirus-induced chitinase in the insect cell endoplasmic reticulum. J Virol, 72:10207–10212.PubMedGoogle Scholar
  77. 77.
    Tiwari P, Saini S, Upmanyu S, et al. 2010. Enhanced expression of recombinant proteins utilizing a modified baculovirus expression vector. Mol Biotechnol, 46:80–89.PubMedCrossRefGoogle Scholar
  78. 78.
    Tjia S T, zu Altenschildesche G M, Doerfler W. 1983. Autographa californica nuclear polyhedrosis virus (AcNPV) DNA does not persist in mass cultures of mammalian cells. Virology, 125:107–117.PubMedCrossRefGoogle Scholar
  79. 79.
    Tomiya N, Betenbaugh M J, Lee Y C. 2003. Humanization of lepidopteran insect-cell-produced glycoproteins. Acc Chem Res, 36:613–620.PubMedCrossRefGoogle Scholar
  80. 80.
    van Oers M M, Thomas A A, Moormann R J, et al. 2001. Secretory pathway limits the enhanced expression of classical swine fever virus E2 glycoprotein in insect cells. J Biotechnol, 86:31–38.PubMedCrossRefGoogle Scholar
  81. 81.
    Venkaiah B, Viswanathan P, Habib S, et al. 2004. An additional copy of the homologous region (hr1) sequence in the Autographa californica multinucleocapsid polyhedrosis virus genome promotes hyperexpression of foreign genes. Biochemistry, 43:8143–8151.PubMedCrossRefGoogle Scholar
  82. 82.
    Viswanathan P, Venkaiah B, Kumar M S, et al. 2003. The homologous region sequence (hr1) of Autographa californica multinucleocapsid polyhedrosis virus can enhance transcription from non-baculoviral promoters in mammalian cells. J Biol Chem, 278:52564–52571.PubMedCrossRefGoogle Scholar
  83. 83.
    Vlak J M, Klinkenberg F A, Zaal K J, et al. 1988. Functional studies on the p10 gene of Autographa californica nuclear polyhedrosis virus using a recombinant expressing a p10-beta-galactosidase fusion gene. J Gen Virol, 69Pt 4):765–776.PubMedCrossRefGoogle Scholar

Copyright information

© Wuhan Institute of Virology, CAS and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Shu-fen Li
    • 1
  • Hua-lin Wang
    • 1
  • Zhi-hong Hu
    • 1
  • Fei Deng
    • 1
  1. 1.State Key Laboratory of Virology and Joint-Lab of Invertebrate Virology, Wuhan Institute of VirologyChinese Academy of SciencesWuhanChina

Personalised recommendations