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. 2016:2016:4302470.
doi: 10.1155/2016/4302470. Epub 2016 Oct 24.

Systematic Identification and Bioinformatic Analysis of MicroRNAs in Response to Infections of Coxsackievirus A16 and Enterovirus 71

Zheng Zhu  1 , Yuhua Qi  1 , Huan Fan  1 , Lunbiao Cui  1 , Zhiyang Shi  1
Affiliations

Systematic Identification and Bioinformatic Analysis of MicroRNAs in Response to Infections of Coxsackievirus A16 and Enterovirus 71

Zheng Zhu et al. Biomed Res Int. 2016.

Abstract

Hand, foot, and mouth disease (HFMD), mainly caused by coxsackievirus A16 (CVA16) and enterovirus 71 (EV71) infections, remains a serious public health issue with thousands of newly diagnostic cases each year since 2008 in China. The mechanisms underlying viral infection, however, are elusive to date. In the present study, we systematically investigated the host cellular microRNA (miRNA) expression patterns in response to CVA16 and EV71 infections. Through microarray examination, 27 miRNAs (15 upregulated and 12 downregulated) were found to be coassociated with the replication process of two viruses, while the expression levels of 15 and 5 miRNAs were significantly changed in CVA16- and EV71-infected cells, respectively. A great number of target genes of 27 common differentially expressed miRNAs were predicted by combined use of two computational target prediction algorithms, TargetScan and MiRanda. Comprehensive bioinformatic analysis of target genes in GO categories and KEGG pathways indicated the involvement of diverse biological functions and signaling pathways during viral infection. These results provide an overview of the roles of miRNAs in virus-host interaction, which will contribute to further understanding of HFMD pathological mechanisms.

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Figures

Figure 1
Figure 1
(a) Agarose gel electrophoresis analysis of total RNA purified from mock-infected and virus-infected RD cells. (b) The alteration of miRNA expression profiles in response to CVA16 and EV71 infection based on microarray analysis.
Figure 2
Figure 2
Quantitative RT-PCR was performed to examine the expression of miRNAs in virus-infected cells. The expression levels were normalized to endogenous U6 small RNA. Fold change compared with control cells was calculated using the equation 2−ΔΔCt. The data was presented as mean ± SD. Six miRNAs (miR-4484, miR-4497, miR-4530, miR-3665, miR-4455, and miR-4443) exhibited significant fold changes in expression levels (P < 0.05).
Figure 3
Figure 3
The target genes were classified to 3 main GO categories. Y-axis represented the percentage of genes in each enriched GO term.
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