MicroRNA Editing Facilitates Immune Elimination of HCMV Infected Cells

PLoS Pathogens

Yoav Livneh¹  Hartmut Hengel²  Albert Zimmermann²  Eithan Galun³  Vu Thuy Khanh Le⁴  Vaclav Horejsi⁵  Ofer Isakov⁶  Noam Shomron⁶  Daphna Nachmani⁷  Ofer Mandelboim⁷  Dana G. Wolf⁸  Esther Oiknine Djian⁸  Yiska Weisblum⁸ 

[1] Department of Neurobiology, Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel;Department of Virology, Institute for Medical Microbiology and Hygiene, Albert-Ludwigs-Universitat, Freiburg, Germany;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;The Lautenberg Center for General and Tumor Immunology, The BioMedical Research Institute Israel Canada of the Faculty of Medicine, The Hebrew University Hadassah Medical School, Jerusalem, Israel;Virology Unit, Hadassah Hospital, The Hebrew University Hadassah Medical School, Jerusalem, Israel

关键词: NK cells;    MicroRNAs;    Cytomegalovirus infection;    Human cytomegalovirus;    Infectious disease control;    Untranslated regions;    RNA sequencing;    Organ cultures;   

DOI  :  10.1371/journal.ppat.1003963

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY