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Kaposi's Sarcoma Herpesvirus microRNAs Target Caspase 3 and Regulate Apoptosis

Suffert, Guillaume and Malterer, Georg and Hausser, Jean and Viiliäinen, Johanna and Fender, Aurélie and Contrant, Maud and Ivacevic, Tomi and Benes, Vladimir and Gros, Frédéric and Voinnet, Olivier and Zavolan, Mihaela and Ojala, Päivi M. and Haas, Juergen G. and Pfeffer, Sébastien. (2011) Kaposi's Sarcoma Herpesvirus microRNAs Target Caspase 3 and Regulate Apoptosis. PLoS Pathogens, Vol. 7, H. 12 , e1002405.

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Official URL: http://edoc.unibas.ch/dok/A6001707

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Abstract

Kaposi's sarcoma herpesvirus (KSHV) encodes a cluster of twelve micro (mi)RNAs, which are abundantly expressed during both latent and lytic infection. Previous studies reported that KSHV is able to inhibit apoptosis during latent infection; we thus tested the involvement of viral miRNAs in this process. We found that both HEK293 epithelial cells and DG75 cells stably expressing KSHV miRNAs were protected from apoptosis. Potential cellular targets that were significantly down-regulated upon KSHV miRNAs expression were identified by microarray profiling. Among them, we validated by luciferase reporter assays, quantitative PCR and western blotting caspase 3 (Casp3), a critical factor for the control of apoptosis. Using site-directed mutagenesis, we found that three KSHV miRNAs, miR-K12-1, 3 and 4-3p, were responsible for the targeting of Casp3. Specific inhibition of these miRNAs in KSHV-infected cells resulted in increased expression levels of endogenous Casp3 and enhanced apoptosis. Altogether, our results suggest that KSHV miRNAs directly participate in the previously reported inhibition of apoptosis by the virus, and are thus likely to play a role in KSHV-induced oncogenesis.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Zavolan, Mihaela
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Public Library of Science
ISSN:1553-7366
e-ISSN:1553-7374
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:13 Oct 2017 07:44
Deposited On:11 Oct 2012 15:18

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