Abstract
With the frequent outbreaks of emerging infectious diseases in recent years, an effective broad-spectrum antiviral drug is becoming an urgent need for global public health. Cholesterol-25-hydroxylase (CH25H) and its enzymatic products 25-hydroxycholesterol (25HC), a well-known oxysterol that regulates lipid metabolism, have been reported to play multiple functions in modulating cholesterol homeostasis, inflammation, and immune responses. CH25H and 25HC were recently identified as exerting broadly antiviral activities, including upon a variety of highly pathogenic viruses such as human immunodeficiency virus (HIV), Ebola virus (EBOV), Nipah virus (NiV), Rift Valley fever virus (RVFV), and Zika virus (ZIKV). The underlying mechanisms for its antiviral activities are being extensively investigated but have not yet been fully clarified. In this study, we summarized the current findings on how CH25H and 25HC play multiple roles to modulate cholesterol metabolism, inflammation, immunity, and antiviral infections. Overall, 25HC should be further studied as a potential therapeutic agent to control emerging infectious diseases in the future.
Highlights
Frequent outbreaks of highly pathogenic viruses are becoming a severe challenge for global public health, and developing novel strategies to control viral infectious diseases is a necessary scientific issue
We summarize the current findings on how CH25H and 25HC play multifaceted functions that are involved in cellular cholesterol metabolism and immunomodulation and direct antiviral effects
In the presence of excessive cholesterols, 25HC binds to membrane-spanning endoplasmic reticulum (ER) protein—Insulin-induced gene 2 (INSIG2) protein to form sterol regulator-binding protein (SREBP)/insulin-induced gene 2 (INSIG2)/SREBP/INSIG22/cleavage activator protein (SCAP) complexes, which are retained on ER and cannot transport to Golgi apparatus, leading to dysregulation of intracellular sterol metabolism [18]
Summary
Frequent outbreaks of highly pathogenic viruses are becoming a severe challenge for global public health, and developing novel strategies to control viral infectious diseases is a necessary scientific issue. During viral infections, the host’s metabolism is often hijacked to meet the needs of viral replication, and marked metabolic changes ensure an optimal environment for the generation of viral offspring Both innate and adaptive immune responses in the host are induced to fight against viral infections [3]. We summarize the current findings on how CH25H and 25HC play multifaceted functions that are involved in cellular cholesterol metabolism and immunomodulation and direct antiviral effects. This knowledge is expected to provide insight for developing potentially therapeutic drug candidates to control emerging and re-emerging infectious diseases
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