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Contrary to other HFMD-causing enterovirus, EV71 can lead to severe neurological complications, even death. MicroRNAs (miRNAs) are small non-coding RNAs that constitute the largest family of gene regulators participating in numerous biological or pathological processes. We previously reported that miR-16-5p increases with severity of HFMD by investigating the expression patterns of host miRNAs in patients with HFMD. However, the mechanisms by which EV71 induces miR-16-5p expression are not clear, and the interaction between EV71 and miR-16-5p is not yet fully understood. Here, we confirmed EV71-induced expression of miR-16-5p both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> and show that upregulation of miR-16-5p by EV71 infection may occur at the posttranscriptional level. Moreover, EV71-induced caspase activation facilitates the processing of pri-miR-16-1. We also revealed that miR-16-5p can promote EV71-induced nerve cells apoptosis through activating caspase-3. In addition, we found that miR-16-5p can inhibit EV71 replication. CCNE1 and CCND1, two important cell cycle regulators, play an important role in the suppression of EV71 replication by miR-16-5p. Therefore, miR-16-5p is a positive feedback regulator in EV71-induced apoptosis and a suppressor of virus replication. These results help in understanding the interaction network between miRNA and EV71 infection and provide a potential target for the development of antiviral therapy.<\/jats:p>","DOI":"10.1038\/s41598-017-16616-7","type":"journal-article","created":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T15:19:13Z","timestamp":1511277553000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["MiR-16-5p mediates a positive feedback loop in EV71-induced apoptosis and suppresses virus replication"],"prefix":"10.1038","volume":"7","author":[{"given":"Caishang","family":"Zheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenhua","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyu","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianliang","family":"Ke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanzhong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,11,27]]},"reference":[{"key":"16616_CR1","doi-asserted-by":"publisher","first-page":"510","DOI":"10.5114\/aoms.2014.43745","volume":"10","author":"Q Wang","year":"2014","unstructured":"Wang, Q. et al. Clinical features of severe cases of hand, foot and mouth disease with EV71 virus infection in China. Arch Med Sci \n                           10, 510\u2013516, https:\/\/doi.org\/10.5114\/aoms.2014.43745 (2014).","journal-title":"Arch Med Sci"},{"key":"16616_CR2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.7883\/yoken.63.229","volume":"63","author":"S Chatproedprai","year":"2010","unstructured":"Chatproedprai, S. et al. Clinical and molecular characterization of hand-foot-and-mouth disease in Thailand, 2008-2009. Jpn J Infect Dis \n                           63, 229\u2013233 (2010).","journal-title":"Jpn J Infect Dis"},{"key":"16616_CR3","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1016\/S1473-3099(10)70194-8","volume":"10","author":"T Solomon","year":"2010","unstructured":"Solomon, T. et al. Virology, epidemiology, pathogenesis, and control of enterovirus 71. Lancet Infect Dis \n                           10, 778\u2013790, https:\/\/doi.org\/10.1016\/S1473-3099(10)70194-8 (2010).","journal-title":"Lancet Infect Dis"},{"key":"16616_CR4","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1007\/BF01317504","volume":"60","author":"M Chumakov","year":"1979","unstructured":"Chumakov, M. et al. Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria. Arch Virol \n                           60, 329\u2013340 (1979).","journal-title":"Arch Virol"},{"key":"16616_CR5","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/BF01314873","volume":"71","author":"G Nagy","year":"1982","unstructured":"Nagy, G., Takatsy, S., Kukan, E., Mihaly, I. & Domok, I. Virological diagnosis of enterovirus type 71 infections: experiences gained during an epidemic of acute CNS diseases in Hungary in 1978. 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