Volume 28, No 2, Feb 2018
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 28 Issue 2, February 2018: 157-171
ORIGINAL ARTICLES
H5N1 influenza virus-specific miRNA-like small RNA increases cytokine production and mouse mortality via targeting poly(rC)-binding protein 2
Xihan Li1, 2, *, Zheng Fu1, *, Hongwei Liang1, *, Yanbo Wang1, *, Xian Qi3, *, Meng Ding1, Xinlei Sun1, Zhen Zhou1,Ying Huang4, Hongwei Gu1, Limin Li1, Xi Chen1, Donghai Li1, Quan Zhao1, Fenyong Liu5, Hua Wang3,Jin Wang1, Ke Zen1, Chen-Yu Zhang1
1State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, Jiangsu 210046, China;
2Central Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210014, China;
3Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu 210009, China;
4Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210023, China;
5 School of Public Health, University of California at Berkeley, Berkeley, CA 94720, USA
Correspondence: Chen-Yu Zhang,E-mail: cyzhang@nju.edu.cn; Ke Zen,E-mail: kzen@nju.edu.cn; Jin Wang,(E-mail: jwang@nju.edu.cn)
Infection of H5N1 influenza virus causes the highest mortality among all influenza viruses. The mechanisms underlying such high viral pathogenicity are incompletely understood. Here, we report that the H5N1 influenza virus encodes a microRNA-like small RNA, miR-HA-3p, which is processed from a stem loop-containing viral RNA precursor by Argonaute 2, and plays a role in enhancing cytokine production during H5N1 infection. Mechanistic study shows that miR-HA-3p targets poly(rC)-binding protein 2 (PCBP2) and suppresses its expression. Consistent with PCBP2 being an important negative regulator of RIG-I/MAVS-mediated antiviral innate immunity, suppression of PCBP2 expression by miR-HA-3p promotes cytokine production in human macrophages and mice infected with H5N1 virus. We conclude that miR-HA-3p is the first identified influenza virus-encoded microRNA-like functional RNA fragment and a novel virulence factor contributing to H5N1-induced 'cytokine storm' and mortality.
10.1038/cr.2018.3
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