Gender-specific alteration of steroid metabolism and its impact on viral replication in a mouse model of hepatitis B virus infection

Autor: Eun-Sook Park, Juhee Won, Sung Hyun Ahn, Ah Ram Lee, Donghyo Lee, Ju-Yeon Moon, Man Ho Choi, Kyun-Hwan Kim
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Animal Cells and Systems, Vol 28, Iss 1, Pp 466-480 (2024)
Druh dokumentu: article
ISSN: 19768354
2151-2485
1976-8354
DOI: 10.1080/19768354.2024.2403569
Popis: Hepatitis B virus (HBV) is a sex-specific pathogen that is more severe in males than in females. Sex disparities in HBV infection have been attributed to hormonal differences between males and females. However, whether HBV infection affects the metabolic signatures of steroid hormones and how these influences viral replication remains unclear. In this study, we investigated whether HBV infection alters steroid metabolism and its effects on HBV replication. Serum samples from male and female mice obtained after the hydrodynamic injection of replication-competent HBV plasmids were subjected to quantitative steroid profiling. Serum steroid levels in mice were analyzed using an in vitro metabolism assay with the mouse liver S9 fraction. The alteration of steroids by HBV infection was observed only in male mice, particularly with significant changes in androgens, whereas no significant hormonal changes were observed in female mice. Among the altered steroids, dehydroepiandrosterone (DHEA) levels increased the most in male mice after HBV infection. An in vitro metabolism assay revealed that androgen levels were significantly reduced in HBV-infected male mice. Furthermore, the genes involved in DHEA biosynthesis were significantly upregulated in HBV-infected male mice. Interestingly, reduced dihydrotestosterone in male mice significantly inhibits viral replication by suppressing HBV promoter activity, suggesting a viral strategy to overcome the antiviral effects of steroid hormones in males. Our data demonstrated that HBV infection can cause sex-specific changes in steroid metabolism.
Databáze: Directory of Open Access Journals
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