4.7 Article

Cellular microRNA-miR-548g-3p modulates the replication of dengue virus

Journal

JOURNAL OF INFECTION
Volume 70, Issue 6, Pages 631-640

Publisher

W B SAUNDERS CO LTD
DOI: 10.1016/j.jinf.2014.12.001

Keywords

Dengue virus; microRNA; miR-548g-3p; Viral replication

Funding

  1. National Mega Project on Major Infectious Disease Prevention [2012ZX10004213]
  2. National Natural Science Foundation of China [81330058, 81272417, 81102370]
  3. Guangdong Recruitment Program of Creative Research Groups [2009010058]
  4. National Science and Technique Major Project [311030, 201305017, 2012ZX09102101-017]
  5. High-Tech Research (863) Projects [2011AA09070201]
  6. Key Science and Technique Research Project of Guangzhou City [12B292060029]
  7. Guangdong Department of Science & Technology Translational Medicine Center grant [2011A080300002]

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Objective: It has been well recognized that microRNA plays a role in the host-pathogen interaction network. The significance of microRNA in the regulation of dengue virus (DENV) replication, however, remains unknown. The objective of our study was to determine the biological function of miR-548g-3p in modulating the replication of dengue virus. Methods: Here we report that employment of a microRNA target search algorithm to analyze the 50 untranslated region (5 ' UTR) consensus sequences of DENV (DENV serotypes 1-4) led to a discovery that miR-548g-3p directly targets the stem loop A promoter element within the 5 ' UTR, a region essential for DENV replication. Real-time PCR was used to measure the expression levels of miR-548g-3p under DENV infection. We performed overexpression and inhibition assays to test the role of miR-548g-3p on DENV replication. The protein and mRNA levels of interferon were measured by ELISA and real-time PCR respectively. Result: We found that overexpression of miR-548g-3p suppressed multiplication of DENV 1, 2, 3 and 4, and that miR-548g-3p was also found to interfere with DENV translation, thereby suppressing the expression of viral proteins. Conclusion: Our results suggest that miR-548g-3p directly regulates DENV replication and warrant further study to investigate the feasibility of microRNA-based anti-DENV approaches. (C) 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

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