TY - JOUR
T1 - Internalization and intracellular retention of CD4 are two separate functions of the human immunodeficiency virus type 1 Nef protein
AU - Giolo, Giorgia
AU - Neri, Francesca
AU - Casartelli, Nicoletta
AU - Potestà, Marina
AU - Belleudi, Francesca
AU - Torrisi, Maria Rosaria
AU - Doria, Margherita
PY - 2007/11
Y1 - 2007/11
N2 - The pathogenic Nef protein of the human immunodeficiency virus type 1 (HIV-1) downregulates CD4 by inducing its endocytosis and by inhibiting the transport of the receptor to the cell membrane. By means of in vivo-selected mutations, we show that L37, P78 and E177 residues of Nef are required for its effect on CD4 internalization and recycling but dispensable for Nef-induced retention and degradation of intracellular CD4. Of note, the function of Nef on the anterograde transport of newly synthesized CD4 molecules is irrelevant in cells with a slow constitutive CD4 turnover such as T cell lines. Moreover, we show that a mutated CD4 that is unresponsive to Nef-mediated endocytosis, CD4LL144AA, is retained intracellularly and degraded by Nef like wild-type CD4. Thus, Nef's abilities to enhance endocytosis and induce intracellular retention of CD4 are mediated by separate protein surfaces and occur through distinct mechanisms.
AB - The pathogenic Nef protein of the human immunodeficiency virus type 1 (HIV-1) downregulates CD4 by inducing its endocytosis and by inhibiting the transport of the receptor to the cell membrane. By means of in vivo-selected mutations, we show that L37, P78 and E177 residues of Nef are required for its effect on CD4 internalization and recycling but dispensable for Nef-induced retention and degradation of intracellular CD4. Of note, the function of Nef on the anterograde transport of newly synthesized CD4 molecules is irrelevant in cells with a slow constitutive CD4 turnover such as T cell lines. Moreover, we show that a mutated CD4 that is unresponsive to Nef-mediated endocytosis, CD4LL144AA, is retained intracellularly and degraded by Nef like wild-type CD4. Thus, Nef's abilities to enhance endocytosis and induce intracellular retention of CD4 are mediated by separate protein surfaces and occur through distinct mechanisms.
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U2 - 10.1099/vir.0.83164-0
DO - 10.1099/vir.0.83164-0
M3 - Article
C2 - 17947540
AN - SCOPUS:36248950722
VL - 88
SP - 3133
EP - 3138
JO - Journal of General Virology
JF - Journal of General Virology
SN - 0022-1317
IS - 11
ER -