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Updated: Jan 19, 2026
Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
Published on: August 23, 2016
Azithromycin Protects against Zika virus Infection by Upregulating virus-induced Type I and III Interferon Responses
Chunfeng Li1,2,3, Shulong Zu4,5, Yong-Qiang Deng2
1Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005; Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China gcheng@mednet.ucla.edu qincf@bmi.ac.cn chunfeng@stanford.edu.
Abstract:
Azithromycin (AZM) is a widely used antibiotic, with additional antiviral and anti-inflammatory properties that remain poorly understood. Although Zika virus (ZIKV) poses a significant threat to global health, there are currently no vaccines or effective therapeutics against it. Herein, we report that AZM effectively suppresses ZIKV infection in vitro by targeting a late stage in the viral life cycle. Besides that, AZM upregulates the expression of host type I and III interferons and several of their downstream interferon-stimulated genes (ISGs) in response to ZIKV infection. In particular, we found that AZM upregulates the expression of MDA5 and RIG-I, pathogen recognition receptors (PRRs) induced by ZIKV infection, and increases the levels of phosphorylated TBK1 and IRF3. Interestingly, AZM treatment upregulates phosphorylation of TBK1, without inducing phosphorylation of IRF3 by itself. These findings highlight the potential use of AZM as a broad antiviral agent to combat viral infection and prevent ZIKV associated devastating clinical outcomes, such as congenital microcephaly.
Insights
Azithromycin (AZM) effectively suppresses Zika virus (ZIKV) infection by targeting a late viral stage. AZM also boosts host antiviral responses, showing potential as a broad-spectrum antiviral agent against ZIKV.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Zika virus (ZIKV) presents a significant global health challenge with no current vaccines or effective treatments.
- Azithromycin (AZM), a common antibiotic, possesses poorly understood antiviral and anti-inflammatory properties.
Purpose of the Study:
- To investigate the antiviral potential of Azithromycin against Zika virus infection.
- To elucidate the mechanisms by which AZM affects ZIKV replication and host antiviral responses.
Main Methods:
- In vitro assessment of AZM's effect on ZIKV infection.
- Analysis of host type I and III interferon and interferon-stimulated gene (ISG) expression.
- Evaluation of pathogen recognition receptor (PRR) and downstream signaling molecule activation.
Main Results:
- AZM significantly suppressed ZIKV infection in vitro by interfering with a late stage of the viral life cycle.
- AZM upregulated host type I and III interferons and ISGs in response to ZIKV.
- AZM enhanced the expression of MDA5 and RIG-I, and increased phosphorylation of TBK1 and IRF3, with TBK1 phosphorylation occurring independently of IRF3.
Conclusions:
- Azithromycin demonstrates potent antiviral activity against ZIKV in vitro.
- AZM enhances host innate immune responses, including interferon production and signaling pathways.
- These findings suggest AZM's potential as a broad-spectrum antiviral therapeutic to mitigate ZIKV-related health issues.
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