Kaposi's sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis.
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...
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Public Library of Science (PLoS)
2011
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oai:doaj.org-article:3e1319a9b25b4d58809a8612eb7109b12021-11-18T06:05:01ZKaposi's sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis.1553-73661553-737410.1371/journal.ppat.1002405https://doaj.org/article/3e1319a9b25b4d58809a8612eb7109b12011-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22174674/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Kaposi'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.Guillaume SuffertGeorg MaltererJean HausserJohanna ViiliäinenAurélie FenderMaud ContrantTomi IvacevicVladimir BenesFrédéric GrosOlivier VoinnetMihaela ZavolanPäivi M OjalaJuergen G HaasSébastien PfefferPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 12, p e1002405 (2011) |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Guillaume Suffert Georg Malterer Jean Hausser Johanna Viiliäinen Aurélie Fender Maud Contrant Tomi Ivacevic Vladimir Benes Frédéric Gros Olivier Voinnet Mihaela Zavolan Päivi M Ojala Juergen G Haas Sébastien Pfeffer Kaposi's sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis. |
description |
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. |
format |
article |
author |
Guillaume Suffert Georg Malterer Jean Hausser Johanna Viiliäinen Aurélie Fender Maud Contrant Tomi Ivacevic Vladimir Benes Frédéric Gros Olivier Voinnet Mihaela Zavolan Päivi M Ojala Juergen G Haas Sébastien Pfeffer |
author_facet |
Guillaume Suffert Georg Malterer Jean Hausser Johanna Viiliäinen Aurélie Fender Maud Contrant Tomi Ivacevic Vladimir Benes Frédéric Gros Olivier Voinnet Mihaela Zavolan Päivi M Ojala Juergen G Haas Sébastien Pfeffer |
author_sort |
Guillaume Suffert |
title |
Kaposi's sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis. |
title_short |
Kaposi's sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis. |
title_full |
Kaposi's sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis. |
title_fullStr |
Kaposi's sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis. |
title_full_unstemmed |
Kaposi's sarcoma herpesvirus microRNAs target caspase 3 and regulate apoptosis. |
title_sort |
kaposi's sarcoma herpesvirus micrornas target caspase 3 and regulate apoptosis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2011 |
url |
https://doaj.org/article/3e1319a9b25b4d58809a8612eb7109b1 |
work_keys_str_mv |
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