Directed expression of the HIV-1 accessory protein Vpu in Drosophila fat-body cells inhibits Toll-dependent immune responses.
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 SCF(beta-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-kappa B (NF-kappa B) signalling pathways between flies and mammals, our results suggest a function for Vpu in the inhibition of host NF-kappa B-mediated innate immune defences and provide a powerful genetic approach for studying Vpu inhibition of NF-kappa B signalling in vivo.
Leulier
François
F
Centre de Génétique Moléculaire-Centre National de la Recherche Scientifique, Batiment 26, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
Marchal
Christelle
C
Miletich
Isabelle
I
Limbourg-Bouchon
Bernadette
B
Benarous
Richard
R
Lemaitre
Bruno
B
D000818:Animals; D030801:Animals, Genetically Modified; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000276:immunology / Q000502:physiology*; D005216:Fat Body / Q000166:cytology / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D007113:Immunity, Innate; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D051193:Toll-Like Receptors; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D054298:Human Immunodeficiency Virus Proteins; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D044767:Ubiquitin-Protein Ligases; D054334:Viral Regulatory and Accessory Proteins; C068721:Tl protein, Drosophila; C110233:slmb protein, Drosophila; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C077938:cact protein, Drosophila