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MiR-103/miR-107 inhibits enterovirus 71 replication and facilitates type I interferon response by regulating SOCS3/STAT3 pathway

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Abstract

Background

Enterovirus71 (EV71), the major cause of hand, foot, and-mouth disease (HFMD), has increasingly become a public health challenge. Type I interferons (IFNs) can regulate innate and adaptive immune responses to pathogens. MicroRNAs (miRNAs) play regulatory roles in host innate immune responses to viral infections. However, the roles of miR-103 and miR-107 in EV71 infection remain unclear.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of miR-103, miR-107, suppressor of cytokine signaling 3 (SOCS3), VP1, IFN-α, and IFN-β. Virus titers were measured by 50% tissue culture infectious dose (TCID50) assay. Western blot assay was conducted to detect the protein levels of VP1, IFN-α, IFN-β, SOCS3, signal transducer and activator of transcription 3 (STAT3), and phospho-STAT3 (p-STAT3). Immunofluorescence assay was used to detect the protein level of VP1. The concentrations of IFN-α and IFN-β were examined by Enzyme-linked immunosorbent assay (ELISA). The interaction between SOCS3 and miR-103/miR-107 was predicted by starBase and verified by dual-luciferase reporter assay and RNA pull-down assay.

Results

MiR-103 and miR-107 were downregulated and SOCS3 was upregulated in serum from patients with EV71 and EV71-infected cells. Overexpression of miR-103 and miR-107 repressed EV71 replication by inhibiting EV71 titers and VP1 expression. Moreover, upregulation of miR-103 and miR-107 enhanced EV71-triggered the production of type I IFNs. In addition, miR-103 and miR-107 directly targeted SOCS3, and SOCS3 upregulation reversed the effects of miR-103 and miR-107 on EV71 replication and type I IFN response. Importantly, miR-103 and miR-107 increased STAT3 phosphorylation by targeting SOCS3 after EV71 infection.

Conclusion

MiR-103 and miR-107 suppressed EV71 replication and increased the production of type I IFNs by regulating SOCS3/STAT3 pathway, which might provide a novel strategy for developing effective antiviral therapy.

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Abbreviations

EV71:

Enterovirus71

HFMD:

Hand, foot, and-mouth disease

IFNs:

I interferons

SOCS3:

Suppressor of cytokine signaling 3

TCID50 :

Tissue culture infectious dose

STAT3:

Signal transducer and activator of transcription 3

p-STAT3:

Phospho-STAT3

ELISA:

Enzyme-linked immunosorbent assay

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Authors and Affiliations

  1. Department of Pediatrics, Binhaiwan Central Hospital of Dongguan, Dongguan, China

    Baizhi Huang, Haiping Chen & Yanbing Zheng

  2. Department of Pediatrics, Binhaiwan Central Hospital of Dongguan, No. 111 Humen Avenue, Humen Town, Dongguan City, 523900, Guangdong Province, China

    Baizhi Huang

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  1. Baizhi Huang
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  2. Haiping Chen
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  3. Yanbing Zheng
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Correspondence to Baizhi Huang.

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The design of this protocol follows the tenets of the Declaration of Helsinki, approved by the Ethics Committee of Binhaiwan Central Hospital of Dongguan.

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Huang, B., Chen, H. & Zheng, Y. MiR-103/miR-107 inhibits enterovirus 71 replication and facilitates type I interferon response by regulating SOCS3/STAT3 pathway. Biotechnol Lett 43, 1357–1369 (2021). https://doi.org/10.1007/s10529-021-03115-z

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  • DOI: https://doi.org/10.1007/s10529-021-03115-z

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