Human Cytomegalovirus miR-UL148D Facilitates Latent Viral Infection by Targeting Host Cell Immediate Early Response Gene 5

PLoS Pathogens

Donghai Li¹  Dihan Zhu¹  Chaoyun Pan¹  Ke Zen¹  Limin Li¹  Yan Wang¹  Chen-Yu Zhang¹  Fenyong Liu² 

[1] Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China;School of Public Health, University of California at Berkeley, Berkeley, California, Unites States of America

关键词: Viral persistence;    latency;    Human cytomegalovirus;    MicroRNAs;    Cytomegalovirus infection;    Host cells;    DNA transcription;    Transfection;    Viral replication;   

DOI  :  10.1371/journal.ppat.1006007

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The mechanisms underlying human cytomegalovirus (HCMV) latency remain incompletely understood. Here, we showed that a HCMV-encoded miRNA, miR-UL148D, robustly accumulates during late stages of experimental latent HCMV infection in host cells and promotes HCMV latency by modulating the immediate early response gene 5 (IER5)-cell division cycle 25B (CDC25B) axis in host cells. miR-UL148D inhibited IER5 expression by directly targeting the three-prime untranslated region(3’UTR) of IER5 mRNA and thus rescued CDC25B expression during the establishment of viral latency. Infection with NR-1ΔmiR-UL148D, a derivative of the HCMV clinical strain NR-1 with a miR-UL148D knockout mutation, resulted in sustained induction of IER5 expression but decreased CDC25B expression in host cells. Mechanistically, we further showed that CDC25B plays an important role in suppressing HCMV IE1 and lytic gene transcription by activating cyclin-dependent kinase 1 (CDK-1). Both gain-of-function and lose-of-function assays demonstrated that miR-UL148D promotes HCMV latency by helping maintain CDC25B activity in host cells. These results provide a novel mechanism through which a HCMV miRNA regulates viral latency.

【 授权许可】

CC BY