Journal Article

Directed expression of the HIV-1 accessory protein Vpu in Drosophila fat-body cells inhibits Toll-dependent immune responses

Marchal, Christelle, Lemaitre, Bruno, Miletich, Isabelle, Leulier, François, Limbourg‐Bouchon, Bernadette, Benarous, Richard

2003

Overview

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 β‐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 .

• Publisher: John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V
• Subject: Animals / Animals, Genetically Modified / Cell Cycle Proteins - genetics / Cell Cycle Proteins - metabolism / DNA-Binding Proteins - metabolism / Drosophila melanogaster / Drosophila melanogaster - anatomy & histology / Drosophila melanogaster - immunology / Drosophila melanogaster - physiology / Drosophila Proteins - genetics / Drosophila Proteins - immunology / Drosophila Proteins - metabolism / Fat Body - cytology / Fat Body - metabolism / Fruits / Gene Expression Regulation, Viral / HIV-1 - genetics / HIV-1 - metabolism / Human immunodeficiency virus 1 / Human Immunodeficiency Virus Proteins / Humans / Immunity, Innate / Mammals / Phosphoproteins - metabolism / Phosphorylation / Receptors, Cell Surface - immunology / Receptors, Cell Surface - metabolism / Scientific Report / Signal Transduction - physiology / Toll-Like Receptors / Ubiquitin-Protein Ligases - genetics / Ubiquitin-Protein Ligases - metabolism / Viral Regulatory and Accessory Proteins - genetics / Viral Regulatory and Accessory Proteins - metabolism