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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.

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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.


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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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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).

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