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Updated: Jul 26, 2025
Evaluation of Zika Virus-specific T-cell Responses in Immunoprivileged Organs of Infected Ifnar1-/- Mice
Published on: October 17, 2018
Metformin restrains ZIKV replication and alleviates virus-induced inflammatory responses in microglia
Xiaofang Wang1, Hui Wang2, Panpan Yi3
1Department of Infectious Disease, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan 410005, China; Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Abstract:
The re-emergence of Zika virus (ZIKV) remains a major public health threat that has raised worldwide attention. Accumulating evidence suggests that ZIKV can cause serious pathological changes to the human nervous system, including microcephaly in newborns. Recent studies suggest that metformin, an established treatment for diabetes may play a role in viral infection; however, little is known about the interactions between ZIKV infection and metformin administration. Using fluorescent ZIKV by flow cytometry and immunofluorescence imaging, we found that ZIKV can infect microglia in a dose-dependent manner. Metformin diminished ZIKV replication without the alteration of viral entry and phagocytosis. Our study demonstrated that metformin downregulated ZIKV-induced inflammatory response in microglia in a time- and dose-dependent manner. Our RNA-Seq and qRT-PCR analysis found that type I and III interferons (IFN), such as IFNα2, IFNβ1 and IFNλ3 were upregulated in ZIKV-infected cells by metformin treatment, accompanied with the downregulation of GBP4, OAS1, MX1 and ISG15. Together, our results suggest that metformin-mediated modulation in multiple pathways may attribute to restraining ZIKV infection in microglia, which may provide a potential tool to consider for use in unique clinical circumstances.
Insights
Metformin reduces Zika virus (ZIKV) replication and inflammation in microglia. This diabetes drug may offer a new strategy against ZIKV neuroinflammation, impacting interferon pathways.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Zika virus (ZIKV) poses a significant public health risk, potentially causing severe neurological damage like microcephaly.
- Metformin, a common diabetes medication, is being investigated for its antiviral properties, but its interaction with ZIKV is unclear.
Purpose of the Study:
- To investigate the effect of metformin on ZIKV infection in microglia.
- To elucidate the mechanisms underlying metformin's potential antiviral activity against ZIKV.
Main Methods:
- Utilized fluorescent ZIKV, flow cytometry, and immunofluorescence imaging to assess ZIKV infection in microglia.
- Performed RNA-sequencing (RNA-Seq) and quantitative reverse transcription PCR (qRT-PCR) to analyze gene expression changes.
Main Results:
- Metformin inhibited ZIKV replication in microglia without affecting viral entry or phagocytosis.
- Metformin dose- and time-dependently reduced ZIKV-induced inflammatory responses.
- Metformin treatment upregulated type I and III interferons (IFN) while downregulating specific interferon-stimulated genes (ISGs).
Conclusions:
- Metformin modulates multiple cellular pathways, including interferon signaling, to restrain ZIKV infection in microglia.
- These findings suggest metformin as a potential therapeutic agent for ZIKV infections, particularly in neurological contexts.
