The HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK signaling.

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...

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Autores principales:	Christelle Marchal, Gérald Vinatier, Matthieu Sanial, Anne Plessis, Anne-Marie Pret, Bernadette Limbourg-Bouchon, Laurent Théodore, Sophie Netter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7c47747566284c8c95a3396c1bc7ae08
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spelling	oai:doaj.org-article:7c47747566284c8c95a3396c1bc7ae082021-11-18T07:23:49ZThe HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK signaling.1932-620310.1371/journal.pone.0034310https://doaj.org/article/7c47747566284c8c95a3396c1bc7ae082012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22479597/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Christelle MarchalGérald VinatierMatthieu SanialAnne PlessisAnne-Marie PretBernadette Limbourg-BouchonLaurent ThéodoreSophie NetterPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e34310 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christelle Marchal Gérald Vinatier Matthieu Sanial Anne Plessis Anne-Marie Pret Bernadette Limbourg-Bouchon Laurent Théodore Sophie Netter The HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK signaling.
description	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.
format	article
author	Christelle Marchal Gérald Vinatier Matthieu Sanial Anne Plessis Anne-Marie Pret Bernadette Limbourg-Bouchon Laurent Théodore Sophie Netter
author_facet	Christelle Marchal Gérald Vinatier Matthieu Sanial Anne Plessis Anne-Marie Pret Bernadette Limbourg-Bouchon Laurent Théodore Sophie Netter
author_sort	Christelle Marchal
title	The HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK signaling.
title_short	The HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK signaling.
title_full	The HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK signaling.
title_fullStr	The HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK signaling.
title_full_unstemmed	The HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK signaling.
title_sort	hiv-1 vpu protein induces apoptosis in drosophila via activation of jnk signaling.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/7c47747566284c8c95a3396c1bc7ae08
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The HIV-1 Vpu protein induces apoptosis in Drosophila via activation of JNK signaling.

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