RT Journal Article T1 Nef-induced Alteration of the Early/Recycling Endosomal Compartment Correlates with Enhancement of HIV-1 Infectivity A1 Rodríguez González, Ricardo A1 Janvier, Katy A1 Hitchin, Douglas A1 Day, John A1 Coleman, Scott A1 Noviello, Colleen A1 Bouchet, Jerome A1 Benmerah, Alexandre A1 Guatelli, John A1 Benichou, Serge AB 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 onearly/recycling endosomal compartments. SN 0021-9258 YR 2005 FD 2005 LK https://hdl.handle.net/20.500.14352/98251 UL https://hdl.handle.net/20.500.14352/98251 LA eng NO Madrid, Ricardo, et al. «Nef-Induced Alteration of the Early/Recycling Endosomal Compartment Correlates with Enhancement of HIV-1 Infectivity». Journal of Biological Chemistry, vol. 280, n.o 6, febrero de 2005, pp. 5032-44. https://doi.org/10.1074/jbc.M401202200. DS Docta Complutense RD 7 abr 2025