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Reference
Citation
Marchal, C., Vinatier, G., Sanial, M., Plessis, A., Pret, A.M., Limbourg-Bouchon, B., Théodore, L., Netter, S. (2012). The HIV-1 Vpu Protein Induces Apoptosis in Drosophila via Activation of JNK Signaling.  PLoS ONE 7(3): e34310.
FlyBase ID
FBrf0218002
Publication Type
Research paper
Abstract

The genome of the human immunodeficiency virus type 1 (HIV-1) encodes the canonical retroviral proteins, as well as additional accessory proteins that enhance the expression of viral genes, the infectivity of the virus and the production of virions. The accessory Viral Protein U (Vpu), in particular, enhances viral particle production, while also promoting apoptosis of HIV-infected human T lymphocytes. Some Vpu effects rely on its interaction with the ubiquitin-proteasome protein degradation system, but the mechanisms responsible for its pro-apoptotic effects in vivo are complex and remain largely to be elucidated.We took advantage of the Drosophila model to study the effects of Vpu activity in vivo. Expression of Vpu in the developing Drosophila wing provoked tissue loss due to caspase-dependent apoptosis. Moreover, Vpu induced expression of the pro-apoptotic gene reaper, known to down-regulate Inhibitor of Apoptosis Proteins (IAPs) which are caspase-antagonizing E3 ubiquitin ligases. Indeed, Vpu also reduced accumulation of Drosophila IAP1 (DIAP1). Though our results demonstrate a physical interaction between Vpu and the proteasome-addressing SLIMB/β-TrCP protein, as in mammals, both SLIMB/βTrCP-dependent and -independent Vpu effects were observed in the Drosophila wing. Lastly, the pro-apoptotic effect of Vpu in this tissue was abrogated upon inactivation of the c-Jun N-terminal Kinase (JNK) pathway. Our results in the fly thus provide the first functional evidence linking Vpu pro-apoptotic effects to activation of the conserved JNK pathway.

PubMed ID
PubMed Central ID
PMC3315533 (PMC) (EuropePMC)
Related Publication(s)
Personal communication to FlyBase

Insertion site of P{Mae-UAS.6.11}Diap1[UY1835]
Netter, 2014.2.26, Insertion site of P{Mae-UAS.6.11}Diap1[UY1835] [FBrf0224219]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    PLoS ONE
    Title
    PLoS ONE
    Publication Year
    2006-
    ISBN/ISSN
    1932-6203
    Data From Reference
    Aberrations (1)
    Alleles (47)
    Genes (27)
    Natural transposons (1)
    Insertions (8)
    Transgenic Constructs (31)