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

Cuimin Wang,1,2 Yuting Huang,3 Lanfeng Li,2 Xizhen Huang,2 Yin Huang,2 Xiang Fang,2 Yu Long1,4 1Department of Obstetrics & Gynecology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Obstetrics & Gynecology, Guangxi Zhuang Autonomous Region People’s Hospital, Guangxi Academy of Medical Sciences, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Department of Obstetrics & Gynecology, Youjiang Medical College for Nationalities, Baise City, Guangxi Zhuang Autonomous Region, People’s Republic of China; 4Medical Simulator Center, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Yu Long, Medical Simulator Center, The First Affiliated Hospital of Guangxi Medical University, No. 22 Shuangyong Road, Qingxiu District, Nanning City, Guangxi Zhuang Autonomous Region, 530021, People’s Republic of China, Tel +86-0771-5337560, Email [email protected]: 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.Keywords: hepatitis B virus, LncRNA, immune signaling, maternal-fetal tissues