Directed expression of the HIV‐1 accessory protein Vpu in Drosophila fat‐body cells inhibits Toll‐dependent immune responses
Open Access
- 12 September 2003
- journal article
- Published by Springer Nature in EMBO Reports
- Vol. 4 (10) , 976-981
Abstract
Human immunodeficiency virus 1 (HIV‐1) expresses several accessory proteins that manipulate various host‐cell processes to achieve optimum replicative efficiency. One of them, viral protein U (Vpu), has been shown to interfere with the cellular degradation machinery through interaction with SCFβ‐TrCP complexes. To learn more about Vpu function in vivo , we used the genetically tractable fruit fly, Drosophila melanogaster . Our results show that the directed expression of Vpu, but not the non‐phosphorylated form, Vpu2/6, in fat‐body cells affects Drosophila antimicrobial responses. In flies, the Toll and Imd pathways regulate antimicrobial‐peptide gene expression. We show that Vpu specifically affects Toll pathway activation by inhibiting Cactus degradation. Given the conservation of the Toll/nuclear factor‐κB (NF‐κB) signalling pathways between flies and mammals, our results suggest a function for Vpu in the inhibition of host NF‐κB‐mediated innate immune defences and provide a powerful genetic approach for studying Vpu inhibition of NF‐κB signalling in vivo .Keywords
This publication has 31 references indexed in Scilit:
- βTrCP-Mediated Proteolysis of NF-κB1 p105 Requires Phosphorylation of p105 Serines 927 and 932Molecular and Cellular Biology, 2003
- The F-box protein Slimb controls the levels of clock proteins Period and TimelessNature, 2002
- Genetic Evidence for the Essential Role of β-Transducin Repeat-containing Protein in the Inducible Processing of NF-κB2/p100Journal of Biological Chemistry, 2002
- Shared Pathways of IκB Kinase-Induced SCFβTrCP-Mediated Ubiquitination and Degradation for the NF-κB Precursor p105 and IκBαMolecular and Cellular Biology, 2001
- A Drosophila IκB kinase complex required for Relish cleavage and antibacterial immunityGenes & Development, 2000
- Phosphorylation Meets Ubiquitination: The Control of NF-κB ActivityAnnual Review of Immunology, 2000
- Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowinJournal of Molecular Biology, 1998
- In Vivo Regulation of the IκB Homologue cactus during the Immune Response of DrosophilaJournal of Biological Chemistry, 1998
- A Novel Human WD Protein, h-βTrCP, that Interacts with HIV-1 Vpu Connects CD4 to the ER Degradation Pathway through an F-Box MotifMolecular Cell, 1998
- The Dorsoventral Regulatory Gene Cassette spätzle/Toll/cactus Controls the Potent Antifungal Response in Drosophila AdultsCell, 1996