MicroRNA editing facilitates immune elimination of HCMV infected cells.

The human cytomegalovirus (HCMV) is extremely prevalent in the human population. Infection by HCMV is life threatening in immune compromised individuals and in immune competent individuals it can cause severe birth defects, developmental retardation and is even associated with tumor development. Whi...

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Main Authors: Daphna Nachmani, Albert Zimmermann, Esther Oiknine Djian, Yiska Weisblum, Yoav Livneh, Vu Thuy Khanh Le, Eithan Galun, Vaclav Horejsi, Ofer Isakov, Noam Shomron, Dana G Wolf, Hartmut Hengel, Ofer Mandelboim
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-02-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003963&type=printable
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author Daphna Nachmani
Albert Zimmermann
Esther Oiknine Djian
Yiska Weisblum
Yoav Livneh
Vu Thuy Khanh Le
Eithan Galun
Vaclav Horejsi
Ofer Isakov
Noam Shomron
Dana G Wolf
Hartmut Hengel
Ofer Mandelboim
author_facet Daphna Nachmani
Albert Zimmermann
Esther Oiknine Djian
Yiska Weisblum
Yoav Livneh
Vu Thuy Khanh Le
Eithan Galun
Vaclav Horejsi
Ofer Isakov
Noam Shomron
Dana G Wolf
Hartmut Hengel
Ofer Mandelboim
author_sort Daphna Nachmani
collection DOAJ
description The human cytomegalovirus (HCMV) is extremely prevalent in the human population. Infection by HCMV is life threatening in immune compromised individuals and in immune competent individuals it can cause severe birth defects, developmental retardation and is even associated with tumor development. While numerous mechanisms were developed by HCMV to interfere with immune cell activity, much less is known about cellular mechanisms that operate in response to HCMV infection. Here we demonstrate that in response to HCMV infection, the expression of the short form of the RNA editing enzyme ADAR1 (ADAR1-p110) is induced. We identified the specific promoter region responsible for this induction and we show that ADAR1-p110 can edit miR-376a. Accordingly, we demonstrate that the levels of the edited-miR-376a (miR-376a(e)) increase during HCMV infection. Importantly, we show that miR-376a(e) downregulates the immune modulating molecule HLA-E and that this consequently renders HCMV infected cells susceptible to elimination by NK cells.
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id doaj-art-e8c1418cb98640ef9ed5e405b2cb6b43
institution DOAJ
issn 1553-7366
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language English
publishDate 2014-02-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Pathogens
spelling doaj-art-e8c1418cb98640ef9ed5e405b2cb6b432025-08-20T03:01:31ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-02-01102e100396310.1371/journal.ppat.1003963MicroRNA editing facilitates immune elimination of HCMV infected cells.Daphna NachmaniAlbert ZimmermannEsther Oiknine DjianYiska WeisblumYoav LivnehVu Thuy Khanh LeEithan GalunVaclav HorejsiOfer IsakovNoam ShomronDana G WolfHartmut HengelOfer MandelboimThe human cytomegalovirus (HCMV) is extremely prevalent in the human population. Infection by HCMV is life threatening in immune compromised individuals and in immune competent individuals it can cause severe birth defects, developmental retardation and is even associated with tumor development. While numerous mechanisms were developed by HCMV to interfere with immune cell activity, much less is known about cellular mechanisms that operate in response to HCMV infection. Here we demonstrate that in response to HCMV infection, the expression of the short form of the RNA editing enzyme ADAR1 (ADAR1-p110) is induced. We identified the specific promoter region responsible for this induction and we show that ADAR1-p110 can edit miR-376a. Accordingly, we demonstrate that the levels of the edited-miR-376a (miR-376a(e)) increase during HCMV infection. Importantly, we show that miR-376a(e) downregulates the immune modulating molecule HLA-E and that this consequently renders HCMV infected cells susceptible to elimination by NK cells.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003963&type=printable
spellingShingle Daphna Nachmani
Albert Zimmermann
Esther Oiknine Djian
Yiska Weisblum
Yoav Livneh
Vu Thuy Khanh Le
Eithan Galun
Vaclav Horejsi
Ofer Isakov
Noam Shomron
Dana G Wolf
Hartmut Hengel
Ofer Mandelboim
MicroRNA editing facilitates immune elimination of HCMV infected cells.
PLoS Pathogens
title MicroRNA editing facilitates immune elimination of HCMV infected cells.
title_full MicroRNA editing facilitates immune elimination of HCMV infected cells.
title_fullStr MicroRNA editing facilitates immune elimination of HCMV infected cells.
title_full_unstemmed MicroRNA editing facilitates immune elimination of HCMV infected cells.
title_short MicroRNA editing facilitates immune elimination of HCMV infected cells.
title_sort microrna editing facilitates immune elimination of hcmv infected cells
url https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1003963&type=printable
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