Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Truncated vesicular stomatitis virus G protein improves baculovirus transduction efficiency in vitro and in vivo

Abstract

Pseudotyping of viral vectors has been widely used to enhance viral transduction efficiency. One of the most popular pseudotyping proteins has been the G-protein of the vesicular stomatitis virus, VSV-G. In the present study, we show that the 21-amino-acid ectodomain with transmembrane and cytoplasmic tail domains of VSV-G (VSV-GED) augments baculovirus-mediated gene delivery in vertebrate cells by aiding viral entry. The VSV-GED pseudotyped virus replicated efficiently in insect cells yielding high titers. Five out of six studied cell lines showed improved transduction, as measured by a number of transduced cells or transgene expression level. Nearly 15-fold increase in the transduction efficiency was detected in rat malignant glioma cells as compared to the control virus. In the rat brain, transgene expression could be detected in the walls of lateral ventricles and in subarachnoid membranes. Increased transduction efficiency was also observed in the rabbit muscle. Our results suggest that VSV-GED enhances baculoviral gene transfer by augmenting gp64-mediated endosomal release. Moreover, no cytotoxicity was associated with improved gene transfer efficiency. Thus, VSV-GED pseudotyping provides a simple means to enhance baculovirus-mediated gene transfer in vitro and in vivo.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Purchase on Springer Link

Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Huser A, Hofmann C . Baculovirus vectors: novel mammalian cell gene-delivery vehicles and their applications. Am J Pharmacogenomics 2003; 3: 53–63.

    Article  CAS  Google Scholar 

  2. Airenne KJ, Hiltunen MO, Turunen MP, Turunen AM, Laitinen OH, Kulomaa MS et al. Baculovirus-mediated periadventitial gene transfer to rabbit carotid artery. Gene Therapy 2000; 7: 1499–1504.

    Article  CAS  Google Scholar 

  3. Pieroni L, Maione D, La Monica N . In vivo gene transfer in mouse skeletal muscle mediated by baculovirus vectors. Hum Gene Ther 2001; 12: 871–881.

    Article  CAS  Google Scholar 

  4. Lehtolainen P, Tyynela K, Kannasto J, Airenne KJ, Yla-Herttuala S . Baculoviruses exhibit restricted cell type specificity in rat brain: a comparison of baculovirus- and adenovirus-mediated intracerebral gene transfer in vivo. Gene Therapy 2002; 9: 1693–1699.

    Article  CAS  Google Scholar 

  5. Tani H, Limn CK, Yap CC, Onishi M, Nozaki M, Nishimune Y et al. In vitro and in vivo gene delivery by recombinant baculoviruses. J Virol 2003; 77: 9799–9808.

    Article  CAS  Google Scholar 

  6. Verhoeyen E, Cosset FL . Surface-engineering of lentiviral vectors. J Gene Med 2004; 6 (Suppl 1): S83–S94.

    Article  CAS  Google Scholar 

  7. Yun CO, Cho EA, Song JJ, Kang DB, Kim E, Sohn JH et al. dl-VSVG-LacZ, a vesicular stomatitis virus glycoprotein epitope-incorporated adenovirus, exhibits marked enhancement in gene transduction efficiency. Hum Gene Ther 2003; 14: 1643–1652.

    Article  CAS  Google Scholar 

  8. Tang J, Yang T, Ghosh HP, Geller AI . Helper virus-free HSV-1 vectors packaged both in the presence of VSV G protein and in the absence of HSV-1 glycoprotein B support gene transfer into neurons in the rat striatum. J Neurovirol 2001; 7: 548–555.

    Article  CAS  Google Scholar 

  9. Quinonez R, Sutton RE . Lentiviral vectors for gene delivery into cells. DNA Cell Biol 2002; 21: 937–951.

    Article  CAS  Google Scholar 

  10. Barsoum J, Brown R, McKee M, Boyce FM . Efficient transduction of mammalian cells by a recombinant baculovirus having the vesicular stomatitis virus G glycoprotein. Hum Gene Ther 1997; 8: 2011–2018.

    Article  CAS  Google Scholar 

  11. Burns JC, Friedmann T, Driever W, Burrascano M, Yee JK . Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells. Proc Natl Acad Sci USA 1993; 90: 8033–8037.

    Article  CAS  Google Scholar 

  12. Ory DS, Neugeboren BA, Mulligan RC . A stable human-derived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus g pseudotypes. Proc Natl Acad Sci USA 1996; 93: 11400–11406.

    Article  CAS  Google Scholar 

  13. Tani H, Nishijima M, Ushijima H, Miyamura T, Matsuura Y . Characterization of cell-surface determinants important for baculovirus infection. Virology 2001; 279: 343–353.

    Article  CAS  Google Scholar 

  14. Park SW, Lee HK, Kim TG, Yoon SK, Paik SY . Hepatocyte-specific gene expression by baculovirus pseudotyped with vesicular stomatitis virus envelope glycoprotein. Biochem Biophys Res Commun 2001; 289: 444–450.

    Article  CAS  Google Scholar 

  15. Robison CS, Whitt MA . The membrane-proximal stem region of vesicular stomatitis virus G protein confers efficient virus assembly. J Virol 2000; 74: 2239–2246.

    Article  CAS  Google Scholar 

  16. Jeetendra E, Robison CS, Albritton LM, Whitt MA . The membrane-proximal domain of vesicular stomatitis virus G protein functions as a membrane fusion potentiator and can induce hemifusion. J Virol 2002; 76: 12300–12311.

    Article  CAS  Google Scholar 

  17. Chapple SD, Jones IM . Non-polar distribution of green fluorescent protein on the surface of Autographa californica nucleopolyhedrovirus using a heterologous membrane anchor. J Biotechnol 2002; 95: 269–275.

    Article  CAS  Google Scholar 

  18. Ojala K, Koski J, Ernst W, Grabherr R, Jones I, Oker-Blom C . Improved display of synthetic IgG-binding domains on the baculovirus surface. Technol Cancer Res Treat 2004; 3: 77–84.

    Article  CAS  Google Scholar 

  19. Sandmair AM, Turunen M, Tyynela K, Loimas S, Vainio P, Vanninen R et al. Herpes simplex virus thymidine kinase gene therapy in experimental rat BT4C glioma model: effect of the percentage of thymidine kinase-positive glioma cells on treatment effect, survival time, and tissue reactions. Cancer Gene Ther 2000; 7: 413–421.

    Article  CAS  Google Scholar 

  20. Hofmann C, Sandig V, Jennings G, Rudolph M, Schlag P, Strauss M . Efficient gene transfer into human hepatocytes by baculovirus vectors. Proc Natl Acad Sci USA 1995; 92: 10099–10103.

    Article  CAS  Google Scholar 

  21. Boyce FM, Bucher NL . Baculovirus-mediated gene transfer into mammalian cells. Proc Natl Acad Sci USA 1996; 93: 2348–2352.

    Article  CAS  Google Scholar 

  22. Kukkonen SP, Airenne KJ, Marjomaki V, Laitinen OH, Lehtolainen P, Kankaanpaa P et al. Baculovirus capsid display: a novel tool for transduction imaging. Mol Ther 2003; 8: 853–862.

    Article  CAS  Google Scholar 

  23. Blissard GW, Wenz JR . Baculovirus gp64 envelope glycoprotein is sufficient to mediate pH-dependent membrane fusion. J Virol 1992; 66: 6829–6835.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Carneiro FA, Stauffer F, Lima CS, Juliano MA, Juliano L, Da Poian AT . Membrane fusion induced by vesicular stomatitis virus depends on histidine protonation. J Biol Chem 2003; 278: 13789–13794.

    Article  CAS  Google Scholar 

  25. Watson DJ, Kobinger GP, Passini MA, Wilson JM, Wolfe JH . Targeted transduction patterns in the mouse brain by lentivirus vectors pseudotyped with VSV, Ebola, Mokola, LCMV, or MuLV envelope proteins. Mol Ther 2002; 5: 528–537.

    Article  CAS  Google Scholar 

  26. Facciabene A, Aurisicchio L, La MN . Baculovirus vectors elicit antigen-specific immune responses in mice. J Virol 2004; 78: 8663–8672.

    Article  CAS  Google Scholar 

  27. Park F, Ohashi K, Kay MA . Therapeutic levels of human factor VIII and IX using HIV-1-based lentiviral vectors in mouse liver. Blood 2000; 96: 1173–1176.

    CAS  PubMed  Google Scholar 

  28. Schauber CA, Tuerk MJ, Pacheco CD, Escarpe PA, Veres G . Lentiviral vectors pseudotyped with baculovirus gp64 efficiently transduce mouse cells in vivo and show tropism restriction against hematopoietic cell types in vitro. Gene Therapy 2004; 11: 266–275.

    Article  CAS  Google Scholar 

  29. Volkman LE, Goldsmith PA . In Vitro Survey of Autographa californica Nuclear Polyhedrosis Virus Interaction with Nontarget Vertebrate Host Cells. Applied and Environmental Microbiology 1983; 45 (3): 1085–1093.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Watson DJ, Passini MA, Wolfe JH . Transduction of the choroid plexus and ependyma in neonatal mouse brain by vesicular stomatitis virus glycoprotein-pseudotyped lentivirus and adeno-associated virus type 5 vectors. Hum Gene Ther 2005; 16: 49–56.

    Article  CAS  Google Scholar 

  31. Raty JK, Airenne KJ, Marttila AT, Marjomaki V, Hytonen VP, Lehtolainen P et al. Enhanced gene delivery by avidin-displaying baculovirus. Mol Ther 2004; 9: 282–291.

    Article  CAS  Google Scholar 

  32. Airenne KJ, Peltomaa E, Hytonen VP, Laitinen OH, Yla-Herttuala S . Improved generation of recombinant baculovirus genomes in Escherichia coli. Nucleic Acids Res 2003; 31: e101.

    Article  Google Scholar 

  33. Turunen MP, Hiltunen MO, Ruponen M, Virkamäki L, Szoka FCJ, Urtti A et al. Efficient adventitial gene delivery to rabbit carotid artery with cationic polymer-plasmid complexes. Gene Therapy 1999; 6: 6–11.

    Article  CAS  Google Scholar 

  34. Zhang SX, Han Y, Blissard GW . Palmitoylation of the Autographa californica multicapsid nucleopolyhedrovirus envelope glycoprotein GP64: mapping, functional studies, and lipid rafts. J Virol 2003; 77: 6265–6273.

    Article  CAS  Google Scholar 

  35. Martinez I, Wertz GW . Biological differences between vesicular stomatitis virus Indiana and New Jersey serotype glycoproteins: identification of amino acid residues modulating pH-dependent infectivity. J Virol 2005; 79: 3578–3585.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to Loy Volkman (University of California, Berkeley, CA, USA) for antibodies against vp39. We thank Tarja Taskinen, Erik Peltomaa, Mervi Nieminen, Riina Kylätie, Riikka Eisto, Tiina Koponen and Seija Sahrio for excellent technical assistance. This work was supported by the Finnish Academy, Sigrid Juselius Foundation and Ark Therapeutics Ltd.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S Ylä-Herttuala.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kaikkonen, M., Räty, J., Airenne, K. et al. Truncated vesicular stomatitis virus G protein improves baculovirus transduction efficiency in vitro and in vivo. Gene Ther 13, 304–312 (2006). https://doi.org/10.1038/sj.gt.3302657

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3302657

Keywords

This article is cited by

Search

Quick links