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Updated: Aug 17, 2025
Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Targeting 7-dehydrocholesterol reductase against EV-A71 replication by upregulating interferon response
Huiqiang Wang1, Boming Cui2, Haiyan Yan1
1CAMS Key Laboratory of Antiviral Drug Research, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science, Beijing, China.
Researchers found that the enzyme 7-dehydrocholesterol reductase (DHCR7) aids enterovirus A71 (EV-A71) replication. Inhibiting DHCR7 or using its precursor 7-dehydrocholesterol (7-DHC) blocked viral growth and protected mice, suggesting a new treatment strategy for enterovirus infections.
Area of Science:
- Virology
- Biochemistry
- Molecular Biology
Background:
- Viral infections can disrupt host cell metabolism.
- Cholesterol synthesis is crucial for cellular processes and can be exploited by viruses.
- 7-dehydrocholesterol reductase (DHCR7) is a key enzyme in cholesterol biosynthesis.
Purpose of the Study:
- To investigate the role of DHCR7 in enterovirus A71 (EV-A71) replication.
- To explore DHCR7 as a potential therapeutic target for enterovirus infections.
Main Methods:
- Studied the effect of DHCR7 overexpression and mutation on EV-A71 replication.
- Utilized siRNA to knockdown DHCR7 expression and AY9944 to inhibit DHCR7 activity.
- Administered AY9944 and 7-dehydrocholesterol (7-DHC) in vitro and in vivo models.
- Assessed the impact on viral replication, host interferon response, and mouse survival.
Main Results:
- DHCR7 overexpression enhanced EV-A71 replication, while its inhibition significantly reduced it.
- Cholesterol supplementation rescued viral replication in DHCR7-inhibited cells.
- AY9944 treatment protected mice from lethal EV-A71 infection and showed efficacy against coxsackievirus B3 and A16.
- AY9944 and 7-DHC promoted IRF3 phosphorylation, activating the interferon response.
Conclusions:
- DHCR7 is essential for EV-A71 replication, acting as a viral dependency factor.
- Pharmacological inhibition of DHCR7 presents a promising therapeutic strategy against enterovirus infections.
- Modulating cholesterol metabolism via DHCR7 offers a novel approach for antiviral treatment.
