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.

  • Letter
  • Published:

A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells

Nature volume 365, pages 666–669 (1993)Cite this article

Abstract

PERMISSIVENESS of the host cell to productive infection by onco-retroviruses is cell-cycle dependent1, and nuclear localization of viral nucleoprotein preintegration complexes will occur only after cells have passed through mitosis2. In contrast, establishment of an integrated provirus after infection by the lentivirus HIV-1 is independent of host cell proliferation3–5. The ability of HIV-1 to replicate in non-dividing cells is partly accounted for by the kary-ophilic properties of the viral preintegration complex which, after virus infection, is actively transported to the host cell nucleus. Here we report that the gag matrix protein of HIV-1 contains a nuclear localization sequence which, when conjugated to a heterologous protein, directs its nuclear import. In addition, HIV-1 mutants containing amino-acid substitutions in this nuclear localization signal integrate and replicate within dividing but not growth-arrested cells, and thus display a phenotype more representative of an onco-retrovirus.

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

Similar content being viewed by others

References

  1. Varmus, H. E. & Swanstrom, R. in RNA Tumor Viruses (eds Weiss, R., Teich, N., Varmus, H. E. & Coffin, J.) 369–512 (Cold Spring Harbor Laboratory Press, New York, 1984).

    Google Scholar 

  2. Roe, T., Reynolds, T. C., Yu, G. & Brown, P. O. EMBO J. 12, 2099–2108 (1993).

    Article  CAS  Google Scholar 

  3. Weinberg, J. B., Mathews, T. J., Cullen, B. R. & Malim, M. H. J. exp. Med. 174, 1477–1482 (1991).

    Article  CAS  Google Scholar 

  4. Bukrinsky, M. I. et al. Proc. natn. Acad. Sci. U.S.A. 89, 6580–6584 (1992).

    Article  ADS  CAS  Google Scholar 

  5. Lewis, P., Hensel, M. & Emerman, M. EMBO. J. 11, 3053–3058 (1992).

    Article  CAS  Google Scholar 

  6. Forbes, D. J. A. Rev. Cell Biol. 8, 495–529 (1992).

    Article  CAS  Google Scholar 

  7. Goldfarb, D. S., Gariepi, J., Schoolnik, G. & Kornberg, R. D. Nature 322, 641–644 (1986).

    Article  ADS  CAS  Google Scholar 

  8. Breeuwer, M. & Goldfarb, D. S. Cell 60, 999–1008 (1990).

    Article  CAS  Google Scholar 

  9. Stevenson, M. et al. J. Virol. 64, 3792–3803 (1990).

    Article  CAS  Google Scholar 

  10. Kimpton, J. & Emerman, M. J. Virol. 66, 2232–2239 (1992).

    Article  CAS  Google Scholar 

  11. Gendelman, H. E. et al. J. Virol. 58, 67–74 (1986).

    Article  CAS  Google Scholar 

  12. Shaw, G. M. et al. Science 226, 1165–1170 (1984).

    Article  ADS  CAS  Google Scholar 

  13. Koenig, S. et al. Science 223, 1089–1093 (1986).

    Article  ADS  Google Scholar 

  14. Wiley, C. A., Schrier, R. D., Nelson, J. A., Lampert, P. W. & Oldstone, M. B. A. Proc. natn. Acad. Sci. U.S.A. 83, 7089–7093 (1986).

    Article  ADS  CAS  Google Scholar 

  15. Price, R. W. et al. Science 239, 586–592 (1988).

    Article  ADS  CAS  Google Scholar 

  16. Haase, A. T. et al. Virology 119, 399–410 (1982).

    Article  CAS  Google Scholar 

  17. Miller, D. G., Adam, M. A. & Miller, A. D. Molec. cell. Biol. 10, 4239–4242 (1990).

    Article  CAS  Google Scholar 

  18. Bowerman, B., Brown, P. O., Bishop, J. M. & Varmus, H. E. Genes Dev. 3, 469–478 (1989).

    Article  CAS  Google Scholar 

  19. Farnet, C. M. & Haseltine, W. A. J. Virol. 65, 1990–1915 (1991).

    Google Scholar 

  20. Bukrinsky, M. I. et al. Proc. natn. Acad. Sci. U.S.A. 90, 6125–6129 (1993).

    Article  ADS  CAS  Google Scholar 

  21. Eliopoulos, E. E. et al. Int. J. biol. Macromol. 4, 263–275 (1982).

    Article  CAS  Google Scholar 

  22. Meyers, G. et al. Human Retroviruses and AIDS (Los Alamos National Laboratory, New Mexico, 1992).

    Google Scholar 

  23. Brown, P. O., Bowerman, B., Varmus, H. E. & Bishop, J. M. Cell 49, 347–356 (1987).

    Article  CAS  Google Scholar 

  24. Hsu, W.-S. & Temin, H. M. Science 250, 1227–1232 (1990).

    Article  ADS  Google Scholar 

  25. Bukrinsky, M. I., Stanwick, T. L., Dempsey, M. P. & Stevenson, M. Science 254, 423–427 (1991).

    Article  ADS  CAS  Google Scholar 

  26. Lori, F. et al. J. Virol. 66, 5067–5074 (1992).

    Article  CAS  Google Scholar 

  27. Trono, D. J. Virol. 66, 4893–4900 (1992).

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Michael I. Bukrinsky

    Present address: Picower Institute for Medical Research, 350 Community Drive, Manhasset, New York, 11030, USA

Authors and Affiliations

  1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, 68198–5120, USA

    Michael I. Bukrinsky, Sheryl Haggerty, Michael P. Dempsey, Natalia Sharova & Mario Stevenson

  2. Eppley Institute for Research, University of Nebraska Medical Center, Omaha, Nebraska, 68198–5120, USA

    Mario Stevenson

  3. Biomolecular Modelling Laboratory, Imperial Cancer Research Fund, London, WC2A 3PX, UK

    Alexei Adzhubei

  4. Department of Biology, University of Rochester, Rochester, New York, 14627, USA

    Lynn Spitz & David Goldfarb

  5. Program in Molecular Medicine, Fred Hutchinson Cancer Center, Seattle, Washington, 98104, USA

    Paul Lewis & Michael Emerman

Authors
  1. Michael I. Bukrinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sheryl Haggerty
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael P. Dempsey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Natalia Sharova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alexei Adzhubei
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lynn Spitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paul Lewis
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David Goldfarb
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Michael Emerman
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mario Stevenson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bukrinsky, M., Haggerty, S., Dempsey, M. et al. A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells. Nature 365, 666–669 (1993). https://doi.org/10.1038/365666a0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/365666a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing