MicroRNA Editing Facilitates Immune Elimination of HCMV Infected Cells

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

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.

Original languageAmerican English
Article numbere1003963
JournalPLoS Pathogens
Volume10
Issue number2
DOIs
StatePublished - Feb 2014

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