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.

VIROLOGY

Hijacking of endocytosis by HIV-1 Nef is becoming crystal clear

The cell surface protein CD4 acts as a coreceptor for incoming HIV particles. However, the expression of CD4 in HIV-producing cells is detrimental to virus propagation and pathogenicity. To solve this issue, the viral accessory protein Nef forces CD4 endocytosis and targets it for lysosomal degradation. Structural elucidation of the AP-2–Nef–CD4 complex shows how Nef connects CD4 to the clathrin endocytic machinery, revealing a potential new target for anti-HIV therapy.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Nef removes HIV-1 receptor CD4 from the cell surface by connecting it to the clathrin endocytic adaptor AP-2.

References

  1. 1.

    Kwon, Y. et al. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-020-0463-z (2020).

  2. 2.

    Kirchhoff, F., Greenough, T. C., Brettler, D. B., Sullivan, J. L. & Desrosiers, R. C. N. Engl. J. Med. 332, 228–232 (1995).

    CAS  Article  Google Scholar 

  3. 3.

    Deacon, N. J. et al. Science 270, 988–991 (1995).

    CAS  Article  Google Scholar 

  4. 4.

    Pereira, E. A. & daSilva, L. L. P. Traffic 17, 976–996 (2016).

    CAS  Article  Google Scholar 

  5. 5.

    Buffalo, C. Z., Iwamoto, Y., Hurley, J. H. & Ren, X. J. Virol. 93, e01322–19 (2019).

    CAS  Article  Google Scholar 

  6. 6.

    Benson, R. E., Sanfridson, A., Ottinger, J. S., Doyle, C. & Cullen, B. R. J. Exp. Med. 177, 1561–1566 (1993).

    CAS  Article  Google Scholar 

  7. 7.

    Ross, T. M., Oran, A. E. & Cullen, B. R. Curr. Biol. 9, 613–621 (1999).

    CAS  Article  Google Scholar 

  8. 8.

    Robinson, M. S. Traffic 16, 1210–1238 (2015).

    CAS  Article  Google Scholar 

  9. 9.

    Chaudhuri, R., Lindwasser, O. W., Smith, W. J., Hurley, J. H. & Bonifacino, J. S. J. Virol. 81, 3877–3890 (2007).

    CAS  Article  Google Scholar 

  10. 10.

    Jin, Y.-J. et al. J. Immunol. 175, 3157–3164 (2005).

    CAS  Article  Google Scholar 

  11. 11.

    Lindwasser, O. W. et al. J. Virol. 82, 1166–1174 (2008).

    CAS  Article  Google Scholar 

  12. 12.

    Chaudhuri, R., Mattera, R., Lindwasser, O. W., Robinson, M. S. & Bonifacino, J. S. J. Virol. 83, 2518–2530 (2009).

    CAS  Article  Google Scholar 

  13. 13.

    Ren, X., Park, S. Y., Bonifacino, J. S. & Hurley, J. H. Elife 3, e01754 (2014).

    Article  Google Scholar 

  14. 14.

    Doray, B., Lee, I., Knisely, J., Bu, G. & Kornfeld, S. Mol. Biol. Cell 18, 1887–1896 (2007).

    CAS  Article  Google Scholar 

  15. 15.

    Noviello, C. M., Benichou, S. & Guatelli, J. C. J. Virol. 82, 1249–1258 (2008).

    CAS  Article  Google Scholar 

  16. 16.

    Wonderlich, E. R., Williams, M. & Collins, K. L. J. Biol. Chem. 283, 3011–3022 (2008).

    CAS  Article  Google Scholar 

  17. 17.

    Jia, X. et al. Nat. Struct. Mol. Biol. 19, 701–706 (2012).

    CAS  Article  Google Scholar 

  18. 18.

    Schaefer, M. R., Wonderlich, E. R., Roeth, J. F., Leonard, J. A. & Collins, K. L. PLoS Pathog. 4, e1000131 (2008).

    Article  Google Scholar 

  19. 19.

    Amorim, N. A. et al. J. Biol. Chem. 289, 27744–27756 (2014).

    CAS  Article  Google Scholar 

  20. 20.

    Tavares, L. A. et al. J. Cell. Sci. 130, 429–443 (2017).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

The work in the authors’ laboratory was supported by the São Paulo Research Foundation (FAPESP, grants 18/00297-7 and 19/02418-9) and the National Council for Scientific and Technological Development (CNPq, 425547/2018-3). L.L.P.d.S. is the recipient of a long-standing investigator scholarship from CNPq. Y.C.J. is supported by a doctoral fellowship from FAPESP (17/12022-0).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Luis L. P. daSilva.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Januário, Y.C., daSilva, L.L.P. Hijacking of endocytosis by HIV-1 Nef is becoming crystal clear. Nat Struct Mol Biol 27, 773–775 (2020). https://doi.org/10.1038/s41594-020-0486-5

Download citation

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