期刊
JOURNAL OF GENERAL VIROLOGY
卷 101, 期 8, 页码 825-839出版社
MICROBIOLOGY SOC
DOI: 10.1099/jgv.0.001441
关键词
dengue; microRNAs; persistent infection; mosquito cells; filamin; innate immune response
资金
- Secretaria de Investigacion y Posgrado of Instituto Politecnico Nacional [20160946, 20181010, 20195702]
- Comision de Operacion y Fomento de Actividades Academicas (COFAA)
- Estimulo al Desempeno de los Investigadores (EDI) of Instituto Politecnico Nacional
- Sistema Nacional de Investigadores (SNI-CONACyT)
- CONACyT
- Programa de Formacion de Investigadores (P.I.F.I.) of Instituto Politecnico Nacional
Dengue virus (DENV) is an important flavivirus that is transmitted to humans by Aedes mosquitoes, where it can establish a persistent infection underlying vertical and horizontal transmission. However, the exact mechanism of persistent DENV infection is not well understood. Recently miR-927 was found to be upregulated in C6/36-HT cells at 57 weeks of persistent infection (C6-L57), suggesting its participation during this type of infection. The aim of this study was to determine the role of miR-927 during infection with DENV type 2. The results indicate an overexpression of miR-927 in C6-L57 cells and acutely infected cells according to the time of infection and the m.o.i. used. The downregulation of miR-927 in C6-L57 cells results in a reduction of both viral titre and viral genome copy number. The overexpression of miR-927 in C6-L40 and C6/36 cells infected at an m.o.i. of 0.1 causes an increase in both viral titre and viral genome copy number, suggesting a pro-viral activity of miR-927. In sitico prediction analysis reveals target mRNAs for miR-927 are implicated in post-translational modifications (SUMO), translation factors (elF-28), the innate immune system (NKIRAS), exocytosis (EXOC-2). endocytosis (APM1) and the cytoskeleton (FLN). The expression levels of FLN were the most affected by both miR-927 overexpression and inhibition, and FLN was determined to be a direct target of miR-927 by a dual-luciferase gene reporter assay. FLN has been associated with the regulation of the Toll pathway and either overexpression or downregulation of miR-927 resulted in expression changes of antimicrobial peptides (Cecropins A and G, and Defensin D) involved in the Toll pathway response.
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