Blot G, Lopez S, Benarous R, Berlioz-Torrent C; IAS Conference on HIV Pathogenesis and Treatment (2nd : 2003 : Paris, France).
Antivir Ther. 2003; 8 (Suppl.1): abstract no. 188.
Department of Infectious Diseases, Institut Cochin, INSERM, CNRS, Universite Rene Descartes, Paris, France
The HIV-1 transmembrane envelope glycoprotein (TMgp41) contains an unusually long intracytoplasmic domain. The TMgp41 intracyto-plasmic domain plays a role in the envelope fusogenicity, the trafficking of envelope into the cell, its incorporation during viral assembly and consequently in the viral infectivity. To identify new cellular partners of the TMgp41 intracytoplasmic domain, we performed a two-hybrid screen using the full length cytoplasmic domain of HIV-1 TMgp41 as the bait and we screened a Jurkat T cell cDNA library. We could identify a new cellular partner of the intra-cytoplasmic tail of the TMgp41: Luman, an ATF/CREB transcription factor, a member of the basic leucine zipper factor superfamily which has the particularity to possess a transmembrane anchor domain. Binding of Luman to the TMgp41 was confirmed by GST pull-down assay and by co-immunoprecipation. Using yeast two-hybrid system, we showed that Luman interacts with the residues 751 to 768 of the TMgp41 and that the central domain of Luman is required for the binding to TMgp41. We demonstrated that expression of the cytoplasmic tail of the TMgp41 in 293T cells inhibits the transactivation activity of Gal4-Luman fusion on Gal4-reporter system. We showed also that overexpression of a truncated form of Luman can inhibit the production of HIV-1 virions and decreased the intracellular expression of the envelope glycoprotein. Lastly, a RNAi against Luman in Hela P4-2 cells increased the replication of HIV-1 virions. This work is supported by INSERM and CNRS and by grants from ANRS, FRM, SIDACTION and Ligue Nationale Contre le Cancer.
Publication Types:
Keywords:
- Animals
- Carrier Proteins
- Cloning, Molecular
- Cyclic AMP Response Element-Binding Protein
- HIV-1
- Trans-Activation (Genetics)
- Transcription Factors
- Virion
- genetics
Other ID:
UI: 102262493
From Meeting Abstracts