Cholesterol 25-hydroxylase suppresses rabies virus infection by inhibiting viral entry
Abstract
Cholesterol-25-hydroxylase (CH25H) is a reticulum-associated membrane protein that catalyzes the oxidation of cholesterol to 25-hydroxycholesterol (25HC). Recent studies have revealed that CH25H is an interferon-stimulated gene (ISG) that suppresses infection by several viruses. In the present study, we found that overexpression of both human and murine CH25H inhibited rabies virus (RABV) infection in HEK-293T (293T) cells. In contrast, silencing of CH25H enhanced RABV replication in 293T cells, and a catalytic mutant of CH25H lost its ability to inhibit RABV infection. Treatment with the oxysterol 25-hydroxycholesterol (25HC), the product of CH25H, dramatically decreased RABV replication in 293T, BSR and N2a cells by inhibiting viral membrane penetration. These data provide insights into the antiviral function of CH25H against RABV infection, which can potentially be used as a therapeutic agent for rabies.
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25-hydroxycholesterol confers broad antiviral activity by blocking entry, replication and production of infectious viruses of diverse enveloped viruses.
“Previous reports have demonstrated that the natural cholesterol metabolite 25-hydroxycholesterol (25-HC), an immune modulator secreted by macrophages during the host response, confers broad antiviral activity by blocking entry, replication and production of infectious viruses of diverse enveloped viruses39–42”
From Peroxisomal very long-chain fatty acid transport is targeted by herpesviruses and the antiviral host response (2022) · cites this paper as [40]
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Weinhofer, I., Buda, A., Kunze, M., Palfi, Z., Traunfellner, M., Hesse, S., Villoria-Gonzalez, A., Hofmann, J., Hametner, S., Regelsberger, G., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03867-y · Cited by 20 · see citing works
- Authors
- Yuan, Y., Wang, Z., Tian, B., Zhou, M., Fu, Z. F., & Zhao, L.
- Affiliations
- University of Georgia (US)
- Corresponding author
- Zhao, Ling
- Venue
- Archives of Virology
- Published
- 2019-09-24
- Volume
- 164
- Issue
- 12
- Pages
- 2963-2974
- ISSN
- 0003-9012 (ISSN-L)
- 0304-8608
- 1432-8798
- OpenAlex
- W2975587160
- Cited by
- 29
- References
- 0
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 8 · 2022: 4 · 2021: 5 · 2020: 4
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Virology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Program for Key Research Projects of China (2016YFD0500400)
- Fundamental Research Funds for the Central Universities (2662015PY227)
- National Natural Science Foundation of China (31522057, 31872451, 31720103917, 31330078)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Rabies epidemiology and control
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- cholesterol 25-hydroxylase, rabies virus, 25-hydroxycholesterol, oxysterols, viral entry inhibition, interferon-stimulated genes, antiviral host factors, cholesterol oxidation
- MeSH terms
- Animals, Cell Line, Humans, Hydroxycholesterols, Rabies, Rabies virus, Steroid Hydroxylases, Virus Replication, Mice, Virus Internalization, Host-Pathogen Interactions
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