TY - JOUR
T1 - Nef-induced alteration of the early/recycling endosomal compartment correlates with enhancement of HIV-1 infectivity
AU - Madrid, Ricardo
AU - Janvier, Katy
AU - Hitchin, Douglas
AU - Day, John
AU - Coleman, Scott
AU - Noviello, Colleen
AU - Bouchet, Jerome
AU - Benmerah, Alexandre
AU - Guatelli, John
AU - Benichou, Serge
PY - 2005/2/11
Y1 - 2005/2/11
N2 - 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.
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 on early/recycling endosomal compartments.
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U2 - 10.1074/jbc.M401202200
DO - 10.1074/jbc.M401202200
M3 - Article
C2 - 15569681
AN - SCOPUS:20044362379
SN - 0021-9258
VL - 280
SP - 5032
EP - 5044
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 6
ER -