Nef-induced alteration of the early/recycling endosomal compartment correlates with enhancement of HIV-1 infectivity

Ricardo Madrid, Katy Janvier, Douglas Hitchin, John Day, Scott Coleman, Colleen Noviello, Jerome Bouchet, Alexandre Benmerah, John Guatelli, Serge Benichou

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


Human immunodeficiency virus type 1 (HIV-1) Nef interacts with the clathrin-associated AP-1 and AP-3 adaptor complexes, stabilizing their association with endosomal membranes. These findings led us to hypothesize a general impact of this viral protein on the endosomal system. Here, we have shown that Nef specifically disturbs the morphology of the early/recycling compartment, inducing a redistribution of early endosomal markers and a shortening of the tubular recycling endosomal structures. Furthermore, Nef modulates the trafficking of the transferrin receptor (TfR), the prototypical recycling surface protein, indicating that it also disturbs the function of this compartment. Nef reduces the rate of recycling of TfR to the plasma membrane, causing TfR to accumulate in early endosomes and reducing its expression at the cell surface. These effects depend on the leucine-based motif of Nef, which is required for the membrane stabilization of AP-1 and AP-3 complexes. Since we show that this motif is also required for the full infectivity of HIV-1 virions, these results indicate that the positive influence of Nef on viral infectivity may be related to its general effects on early/recycling endosomal compartments.

Original languageEnglish (US)
Pages (from-to)5032-5044
Number of pages13
JournalJournal of Biological Chemistry
Issue number6
StatePublished - Feb 11 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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