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Honeysuckle-encoded microRNA2911 inhibits Enterovirus 71 replication via targeting VP1 gene
Xihan Li1, Ying Huang2, Menghuai Sun3
1Central Laboratory, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Affiliated with Nanjing University of Chinese Medicine, Nanjing, China.
Abstract:
Enterovirus 71 (EV71) is the primary pathogen of hand-foot-and-mouth disease (HFMD) in children and virus infections are associated with severe neurological dysfunctions and even death. MIR2911 is a honeysuckle-encoded atypical microRNA with extreme stability. Here, we report that MIR2911 directly inhibits EV71 replication by targeting the VP1 gene. Bioinformatics prediction and luciferase reporter assay showed that MIR2911 could target the VP1 gene of EV71. Transfection experiments using synthetic MIR2911 and extracted RNA from HS decoction shown that each of these preparations was capable of inhibiting EV71 VP1 protein expression; however, these preparations did not impact EV71 mutants in which the MIR2911-binding sites were mutated. Furthermore, EV71 replication was increased by antagomirs against MIR2911 in the HS decoction, implying that MIR2911 was physiologically functional in controlling EV71 replication in vitro. These results indicated that, by targeting VP1 gene, MIR2911 may effectively inhibit EV71 replication. Our results also provide a potential novel strategy on the therapy and/or prevention of HFMD originating from EV71 virus infection.
Insights
Honeysuckle-derived MIR2911 microRNA effectively inhibits Enterovirus 71 (EV71) replication by targeting its VP1 gene. This discovery offers a promising new strategy for preventing and treating hand-foot-and-mouth disease (HFMD) caused by EV71.
Area of Science:
- Virology
- Molecular Biology
- Biochemistry
Background:
- Enterovirus 71 (EV71) is a major cause of hand-foot-and-mouth disease (HFMD) in children, often leading to severe neurological complications and fatalities.
- MIR2911, a stable microRNA encoded by honeysuckle, has shown potential antiviral properties.
Purpose of the Study:
- To investigate the direct antiviral mechanism of MIR2911 against EV71.
- To determine if MIR2911 targets the VP1 gene of EV71 and inhibits viral replication.
Main Methods:
- Bioinformatics prediction and luciferase reporter assays to identify MIR2911's target gene.
- In vitro transfection experiments using synthetic MIR2911 and honeysuckle (HS) decoction to assess inhibition of EV71 VP1 protein expression and replication.
- Utilizing mutated EV71 strains and MIR2911 antagomirs to confirm the specificity and physiological relevance of MIR2911's action.
Main Results:
- MIR2911 was confirmed to directly target the VP1 gene of EV71.
- Both synthetic MIR2911 and HS decoction significantly inhibited EV71 VP1 protein expression and viral replication.
- Inhibition was specific to the MIR2911-binding site, as mutated EV71 strains were unaffected.
- Antagomirs against MIR2911 increased EV71 replication, confirming MIR2911's endogenous antiviral role.
Conclusions:
- MIR2911 effectively inhibits EV71 replication by targeting the VP1 gene.
- MIR2911 represents a potential therapeutic and preventive strategy against EV71-induced HFMD.
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