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MicroRNA editing facilitates immune elimination of HCMV infected cells
D. Nachmani, A. Zimmermann, E. Oiknine Djian, Y. Weisblum, Y. Livneh, VT. Khanh Le, E. Galun, V. Horejsi, O. Isakov, N. Shomron, DG. Wolf, H. Hengel, O. Mandelboim,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
NLK
Directory of Open Access Journals
od 2005
Free Medical Journals
od 2005
Public Library of Science (PLoS)
od 2005
PubMed Central
od 2005
Europe PubMed Central
od 2005
ProQuest Central
od 2005-09-01
Open Access Digital Library
od 2005-09-01
Open Access Digital Library
od 2005-01-01
Open Access Digital Library
od 2005-01-01
Medline Complete (EBSCOhost)
od 2005-09-01
Health & Medicine (ProQuest)
od 2005-09-01
ROAD: Directory of Open Access Scholarly Resources
od 2005
- MeSH
- adenosindeaminasa genetika MeSH
- buňky NK imunologie MeSH
- cytomegalovirové infekce genetika imunologie MeSH
- Cytomegalovirus MeSH
- editace RNA genetika MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- proteiny vázající RNA MeSH
- western blotting MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
Goldyne Savad Institute of Gene Therapy Hadassah Hebrew University Medical Center Jerusalem Israel
Institute for Virology of the University Hospital Essen University Duisburg Essen Essen Germany
Institute of Molecular Genetics Academy of Sciences of the Czech Republic Prague Czech Republic
Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel
Virology Unit Hadassah Hospital The Hebrew University Hadassah Medical School Jerusalem Israel
Citace poskytuje Crossref.org
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- $a 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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