Metformin restrains ZIKV replication and alleviates virus-induced inflammatory responses in microglia

Xiaofang Wang, Hui Wang, Panpan Yi, Coleman Baker, Gonzales Casey, Xuping Xie, Huanle Luo, Jiyang Cai, Xuegong Fan, Lynn Soong, Haitao Hu, Pei-Yong Shi, Yuejin Liang, Jiaren Sun

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish (US)
Article number110512
JournalInternational Immunopharmacology
StatePublished - Aug 2023


  • Inflammation
  • Interferon
  • Metformin
  • Microglia
  • Viral infection
  • ZIKV

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology


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