Park, Eun-Sook Won, Juhee Ahn, Sung Hyun Lee, Ah Ram Lee, Donghyo Moon, Ju-Yeon Choi, Man Ho Kim, Kyun-Hwan 2024-10-02T09:30:22Z 2024-10-02T09:30:22Z 2024-10-02 2024-09 1976-8354 https://pubs.kist.re.kr/handle/201004/150692 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. English 한국통합생물학회 Gender-specific alteration of steroid metabolism and its impact on viral replication in a mouse model of hepatitis B virus infection Article 10.1080/19768354.2024.2403569 1 Animal Cells and Systems, v.28, no.1, pp.466 - 480 Animal Cells and Systems 28 1 466 480 Y scie scopus kci ART003147407 001314452400001 2-s2.0-85204716107 Cell Biology Zoology Cell Biology Zoology Article RECEPTOR ANDROGEN LIVER RISK IDENTIFICATION CHOLESTEROL ALPHA Hepatitis B virus (HBV) dihydrotestosterone steroid profiling gender-specific alteration androgens