Internalization and intracellular retention of CD4 are two separate functions of the human immunodeficiency virus type 1 Nef protein

Giorgia Giolo, Francesca Neri, Nicoletta Casartelli, Marina Potestà, Francesca Belleudi, Maria Rosaria Torrisi, Margherita Doria

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)3133-3138
Number of pages6
JournalJournal of General Virology
Volume88
Issue number11
DOIs
Publication statusPublished - Nov 2007

ASJC Scopus subject areas

  • Immunology
  • Virology

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