Exosomal lncRNA HOTTIP Mediates Antiviral Effect of Tenofovir Alafenamide (TAF) on HBV Infection

Abstract

Qing-Min Liu,1,* Yi-Yu He,2,* Li-Li Liu,3 Li-Kun Wang4 1Intensive Care Unit, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China; 2Department of Cardiovascular Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 3Department of Pathology, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China; 4Infection Control Center, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Li LiuDepartment of Pathology, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of ChinaEmail [email protected] WangInfection Control Center, Linyi People’s Hospital, Linyi, Shandong Province, People’s Republic of ChinaEmail [email protected]: Chronic hepatitis B (CHB) virus (HBV) infection has emerged as a global health burden affecting nearly 292 million people. Tenofovir alafenamide (TAF) is an effective treatment for CHB patients. However, the detailed mechanism underlying the antiviral activity of TAF remains unclear.Methods: In this study, we investigated the antiviral effect of exosomes derived from the serum of CHB patients treated with TAF (Exo-serum) and TAF-treated macrophages (MP) (Exo-MP(TAF)).Results: RNAseq analysis was also performed to determine the associated long non-coding RNAs (lncRNAs). The results demonstrated that both Exo-serum and Exo-MP(TAF) could be taken up by HepAD38 cells and exhibited potent antiviral activities, as manifested by significantly downregulating the levels of hepatitis B surface antigen, hepatitis B e antigen, HBV DNA, and covalently closed circular DNA. The antiviral effect of Exo-serum was more potent than those of TAF treatment alone. RNAseq analysis revealed that lncRNA HOTTIP was upregulated significantly in Exo-serum. Further, lncRNA HOTTIP knockdown reversed the antiviral effect of Exo-MP(TAF) on HepAD38 cells, whereas lncRNA HOTTIP knockdown exerted the opposite roles.Discussion: Taken together, these results suggest that exosomal lncRNA HOTTIP is essential for the antiviral activity of TAF and provide a novel understanding of the exosome-mediated mechanism underlying HBV infection.Keywords: chronic hepatitis B, tenofovir alafenamide, exosome, lncRNA HOTTIP

Keywords

• chronic hepatitis b
• tenofovir alafenamide
• exosome
• lncrna hottip