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VIROLOGY

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

Nature Structural & Molecular Biology volume 27, pages 773–775 (2020)Cite this article

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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.

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

References

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

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  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).

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  1. Center for Virology Research and Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

    Yunan C. Januário & Luis L. P. daSilva

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  1. Yunan C. Januário
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  2. Luis L. P. daSilva
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Correspondence to Luis L. P. daSilva.

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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

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