Antiviral Therapy-Induced Changes in Long Non-Coding RNA Expression Profiles in Umbilical Cord Blood and Placental Tissues of Hepatitis B Virus-Infected Pregnant Women

抗病毒治疗引起的乙型肝炎病毒感染孕妇脐带血和胎盘组织中长链非编码RNA表达谱的变化

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Abstract

BACKGROUND: Hepatitis B virus (HBV) is a major global health concern, with maternal-fetal transmission being the primary route of transmission, which can lead to chronic HBV infection in newborns. Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation and immune responses, but their involvement in HBV transmission during pregnancy remains unclear. This study aimed to assess the impact of tenofovir disoproxil fumarate (TDF)-based antiviral therapy on lncRNA expression profiles and immune signaling pathways in umbilical cord blood and placental tissues and to identify potential therapeutic targets for preventing intrauterine HBV infection. MATERIALS AND METHODS: Umbilical cord serum and placental tissues were collected from six HBV carriers. Three carriers received TDF-based antiviral therapy, and the remaining carriers who did not receive antiviral therapy served as controls. LncRNA microarray analysis and bioinformatics were used to evaluate the effects of antiviral therapy on lncRNA expression profiles and signaling pathways. RESULTS: Antiviral therapy exerted minimal effects on lncRNA expression profiles in umbilical cord blood. In placental tissues, significant alterations in lncRNA expression profiles were observed, including 249 upregulated and 381 downregulated lncRNAs. Antiviral therapy activated innate immune pathways, such as intracellular DNA sensing, chemokine signaling, type I interferon, Jak-Stat, and interferon-γ-mediated adaptive immunity. Through intersection analysis, CPED1 was found differentially expressed in both cord blood and placental tissues. KEGG pathway analysis suggested that low CPED1 expression may inhibit virus transmission via the JAK-STAT pathway. CONCLUSION: This study demonstrated that TDF-based antiviral therapy altered lncRNA expression and activated immune signaling pathways in placental tissues, offering insights into the molecular mechanisms of maternal-fetal HBV transmission.

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