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.

  • Short Communication
  • Published:

Foamy virus as a gene transfer vector to the central nervous system

Gene Therapy volume 16, pages 448–452 (2009)Cite this article

Abstract

Engineered foamy virus (FV) vectors have been lauded for their superior safety profiles and stable integration patterns compared to their gammaretroviral counterparts. The drawback has been the belief that FV incorporation is cell cycle-dependent, thereby limiting its utility in post-mitotic tissues such as the central nervous system. In this brief communication, we challenged this theory by examining FV in vivo. We injected equal titers of FV and lentivirus (LV) into the adult rat brain and found that at 1 week, FV transduced a significantly greater volume of bromodeoxyuridine (BrdU)-negative brain parenchyma than did LV. By 8 weeks, however, the volume of transduced tissue was greatly reduced—comparable to LV—and restricted to BrdU+. Taken together, these data implicate a role for FV in short-term gene delivery strategies to the CNS.

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
Buy now

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Trobridge G, Josephson N, Vassilopoulos G, Mac J, Russell DW . Improved foamy virus vectors with minimal viral sequences. Mol Ther 2002; 6: 321–328.

    Article  CAS  PubMed  Google Scholar 

  2. Hooks JJ, Gibbs Jr CJ . The foamy viruses. Bacteriol Rev 1975; 39: 169–185.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Schweizer M, Turek R, Hahn H, Schliephake A, Netzer KO, Eder G et al. Markers of foamy virus infections in monkeys, apes, and accidentally infected humans: appropriate testing fails to confirm suspected foamy virus prevalence in humans. AIDS Res Hum Retroviruses 1995; 11: 161–170.

    Article  CAS  PubMed  Google Scholar 

  4. Flacone V, Schweizer M, Neumann-Haefelin D . Replication of primate foamy viruses in natural and experimental hosts. Curr Top Microbiol Immunol 2003; 277: 161–180.

    Google Scholar 

  5. Heneine W, Schweizer M, Sandsrtrom P, Folks T . Human infection with foamy viruses. Curr Top Microbiol Immunol 2003; 277: 181–196.

    CAS  PubMed  Google Scholar 

  6. Yu SF, Baldwin DN, Gwynn WR, Yendapalli S, Linial ML . Human foamy virus replication: a pathway distinct from that of retrovirus and hepadnaviruses. Science 1996; 271: 1579–1582.

    Article  CAS  PubMed  Google Scholar 

  7. Saib A, Puvion-Dutilleul F, Schmid M, Peries J, The HD . Nuclear targeting of incoming human foamy virus Gag proteins involves a centriolar step. J Virol 1997; 71: 1155–1161.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Hacein-Bay-Abina S, von Kalle C, Schmidt M, Le Deist F, Wulffraat N, McIntyre E et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 2003; 348: 255–256.

    Article  Google Scholar 

  9. Schroder AR, Shinn P, Chen H, Berry C, Ecker JR, Bushman F . HIV-1 integration in the human genome favors active genes and local hotspots. Cell 2002; 110: 521–529.

    Article  CAS  PubMed  Google Scholar 

  10. Wu X, Li Y, Crise B, Burgess SM . Transcription start regions in the human genome are favored targets for MLV integration. Science 2003; 300: 1749–1751.

    Article  CAS  PubMed  Google Scholar 

  11. Trobridge GD, Miller DG, Jacobs MA, Allen JM, Kiem HP, Kaul R et al. Foamy virus vector integration sites in normal human cells. Proc Natl Acad Sci USA 2006; 103: 1498–1503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Josephson NC, Vassilopoulos G, Trobridge GD, Priestley GV, Wood BL, Papayannopoulou T et al. Transduction of human NOD/SCID-repopulating cells with both lymphoid and myeloid potential by foamy virus vectors. Proc Natl Acad Sci USA 2002; 99: 8295–8300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Liu W, He X, Cao Z, Sheng J, Liu H, Li Z et al. Efficient therapeutic gene expression in cultured rat hippocampal neurons mediated by human foamy virus vectors: a potential for the treatment of neurological diseases. Intervirology 2005; 48: 329–335.

    Article  CAS  PubMed  Google Scholar 

  14. Mergia A, Chari S, Kolson DL, Goodenow MM, Ciccarone T . The efficiency of simian foamy virus vector type-1 (SFV-1) in nondividing cells and in human PBLs. Virology 2001; 280: 243–252.

    Article  CAS  PubMed  Google Scholar 

  15. Kiem HP, Allen J, Trobridge G, Olson E, Keyser K, Peterson L et al. Foamy-virus-mediated gene transfer to canine repopulating cells. Blood 2007; 109: 65–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Trobridge G, Russell DW . Cell cycle requirements for transduction by foamy virus vectors compared to those of oncovirus and lentivirus vectors. J Virol 2004; 78: 2327–2335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Coleman JE, Huentelman MJ, Kasparov S, Metcalfe BL, Paton JFR, Katovich MJ et al. Efficient large-scale production and concentration of HIV-1-based lentiviral vectors for use in vivo. Physiol Genomics 2003; 12: 221–228.

    Article  CAS  PubMed  Google Scholar 

  18. Russell DW, Miller AD . Foamy virus vectors. J Virol 1996; 70: 217–222.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Steffens S, Tebbets J, Kramm CM, Lindemann D, Flake A, Sena-Esteves M . Transduction of human glial and neuronal tumor cells with different lentiviral vector pseudotypes. J Neurooncol 2004; 70: 281–288.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This research was supported by NIH Grant nos. NS-36674-08 and 30800-14 to RHM.

Author information

Authors and Affiliations

  1. Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    A V Caprariello & R H Miller

  2. Spinal Cord Injury Division, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA

    S M Selkirk

Authors
  1. A V Caprariello
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R H Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S M Selkirk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S M Selkirk.

Additional information

Conflict of interest

The authors state no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Caprariello, A., Miller, R. & Selkirk, S. Foamy virus as a gene transfer vector to the central nervous system. Gene Ther 16, 448–452 (2009). https://doi.org/10.1038/gt.2008.171

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gt.2008.171

Keywords

This article is cited by

Search

Advanced search

Quick links