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Updated: May 31, 2026
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
miRNA-431-5p enriched in EVs derived from IFN-β stimulated MSCs potently inhibited ZIKV through CD95 downregulation
Meng Yuan1, Xiaoyan Tian1, Wenyuan Ma1
1Center for Public Health Research, Medical School, Nanjing University, Nanjing, 210093, China.
Background:
Zika virus (ZIKV) primarily spreads through mosquito bites and can lead to microcephaly in infants and Guillain-Barre syndrome in adults. It is noteworthy that ZIKV can persist in the semen of infected males for extended periods and can be sexually transmitted. Infection with ZIKV has severe pathological manifestations on the testicular tissues of male mice, resulting in reduced sperm motility and fertility. However, there are no approved prophylactic vaccines or therapeutics available to treat Zika virus infection.
Methods:
Using a male type I and II interferon receptor-deficient (ifnar1(-/-) ifngr1(-/-)) C57BL/6 (AG6) mouse model infected with ZIKV as a representative model, we evaluated the degree of testicular damage and viral replication in various organs in mice treated with EVs derived from MSC-stimulated with IFN-β (IFNβ-EVs) and treated with controls. We measured testicle size, detected viral load in various organs, and analyzed gene expression to assess treatment efficacy.
Results:
Our findings demonstrated that intravenous administration of IFNβ-EVs effectively suppressed ZIKV replication in the testes. Investigation with in-depth RNA sequencing analysis found that IFN-β treatment changed the cargo miRNA of EVs. Notably, miR-431-5p was identified to be significantly enriched in IFNβ-EVs and exhibited potent antiviral activity in vitro. We showed that CD95 was a direct downstream target for miR-431-5p and played a role in facilitating ZIKV replication. miR-431-5p effectively downregulated the expression of CD95 protein, consequently promoted the phosphorylation and nuclear localization of NF-kB, which resulted in the activation of anti-viral status, leading to the suppression of viral replication.
Conclusions:
Our study demonstrated that the EVs produced by IFNβ-treated MSCs could effectively convey antiviral activity.
Insights
IFNβ-EVs effectively suppressed Zika virus replication in male mice testes. This novel therapy utilizes microRNAs to activate antiviral defenses, offering a potential treatment for ZIKV infection.
Area of Science:
- Virology
- Immunology
- Nanomedicine
Background:
- Zika virus (ZIKV) causes microcephaly and Guillain-Barre syndrome.
- ZIKV persists in semen, leading to sexual transmission and male infertility.
- No approved vaccines or therapeutics exist for ZIKV infection.
Purpose of the Study:
- To evaluate the efficacy of IFNβ-EVs in treating ZIKV-induced testicular damage.
- To investigate the antiviral mechanisms of IFNβ-EVs in a mouse model.
Main Methods:
- Utilized a ZIKV-infected interferon receptor-deficient mouse model.
- Administered EVs derived from IFN-β-stimulated MSCs (IFNβ-EVs).
- Assessed testicular size, viral load, and gene expression.
Main Results:
- IFNβ-EVs significantly suppressed ZIKV replication in testes.
- miR-431-5p, enriched in IFNβ-EVs, showed potent in vitro antiviral activity.
- miR-431-5p targeted CD95, activating NF-kB and antiviral status.
Conclusions:
- EVs from IFNβ-treated MSCs effectively deliver antiviral activity.
- This approach shows promise for developing ZIKV therapeutics.
