Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 3133-3138 |
| Number of pages | 6 |
| Journal | Journal of General Virology |
| Volume | 88 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - Nov 2007 |
Fingerprint
ASJC Scopus subject areas
- Immunology
- Virology
Cite this
Internalization and intracellular retention of CD4 are two separate functions of the human immunodeficiency virus type 1 Nef protein. / Giolo, Giorgia; Neri, Francesca; Casartelli, Nicoletta; Potestà, Marina; Belleudi, Francesca; Torrisi, Maria Rosaria; Doria, Margherita.
In: Journal of General Virology, Vol. 88, No. 11, 11.2007, p. 3133-3138.Research output: Contribution to journal › Article
}
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.
UR - http://www.scopus.com/inward/record.url?scp=36248950722&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36248950722&partnerID=8YFLogxK
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 -