Let-7c overexpression inhibits dengue virus replication in human hepatoma Huh-7 cells

• Published in: Virus research Vol. 196; pp. 105 - 112
• Main Authors: Escalera-Cueto, Manuel, Medina-Martínez, Ingrid, del Angel, Rosa M., Berumen-Campos, Jaime, Gutiérrez-Escolano, Ana Lorena, Yocupicio-Monroy, Martha
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 22.01.2015
• Subjects: BACH1; Basic-Leucine Zipper Transcription Factors - genetics; Binding Sites; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; Cell Line, Tumor; Dengue virus; Dengue Virus - genetics; Dengue Virus - metabolism; Fanconi Anemia Complementation Group Proteins - genetics; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Genome, Viral; Heme Oxygenase-1 - genetics; Host-Pathogen Interactions - genetics; Humans; Let-7c; MicroRNAs - genetics; miRNAs; Reproducibility of Results; RNA Interference; RNA, Viral; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Time Factors; Transfection; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - metabolism; Virus Replication - genetics; Let-7c; miRNAs; Dengue virus; BACH1
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2014.11.010

•We obtained the expression profile of miRNAs in dengue virus infection in liver cells.•Let-7c is overexpressed in liver cells infected with DENV-2 and DENV-4.•Let-7c inhibits DENV infection.•BACH1 is down-regulated in liver cells infected with DENV probably through the inhibitory effect of let-7c.•HO-1 is overexpressed in DENV infection presumptively by BACH1 derepression. MicroRNAs (miRNAs) constitute an important class of non-coding RNA implicated in gene expression regulation. More than 1900 miRNA molecules have been identified in humans and their modulation during viral infection and it is recognized to play a role in latency regulation or in establishing an antiviral state. The liver cells are targets during DENV infection, and alteration of liver functions contributes to severe disease. In this work the miRNAs expression profile of the human hepatoma cell line, Huh-7, infected with DENV-2 was determined using microarray and real-time PCR. Let-7c is one of the miRNAs up-regulated during DENV infection in the hepatic Huh-7 as well as in the macrophage-monocytic cell line U937-DC-SIGN. Let-7c overexpression down-regulates both DENV-2 and DENV-4 infection. Additionally, we found that the transcription factor BACH1, a let-7c target, is also down-regulated during DENV infection. In accordance with this finding, HO-1, the main responsive factor of BACH1 was found up-regulated. The up-regulation of HO-1 may contribute to the stress oxidative response in infected cells.