Exosomal lncRNA HOTTIP Mediates Antiviral Effect of Tenofovir Alafenamide (TAF) on HBV Infection.
Exosomal lncRNA HOTTIP Mediates Antiviral Effect of Tenofovir Alafenamide (TAF) on HBV Infection.
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外泌体 lncRNA HOTTIP 介导替诺福韦艾拉酚胺 (TAF) 对 HBV 感染的抗病毒作用
DOI：
10.2147/jir.s315716
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发表时间：
2021
影响因子：
4.5
通讯作者：
Wang LK
中科院分区：
文献类型：
--
作者：
Liu QM;He YY;Liu LL;Wang LK
慢性B型肝炎（CH B）病毒（HBV）感染已成为影响近2.92亿人的全球健康负担。替诺福韦艾拉酚胺（TAF）是治疗慢性乙型肝炎的有效药物。然而，TAF抗病毒活性的详细机制仍不清楚。在这项研究中，我们研究了来源于用TAF（Exo-serum）和TAF处理的巨噬细胞（MP）（Exo-MP（TAF））治疗的CHB患者血清的外泌体的抗病毒作用。还进行RNAseq分析以确定相关的长非编码RNA（lncRNA）。结果表明，Exo-serum和Exo-MP（TAF）均能被HepAD 38细胞摄取，并表现出较强的抗病毒活性，表现为显著下调B表面抗原、B e抗原、HBV DNA和共价闭合环状DNA的水平。Exo血清的抗病毒作用比TAF单独治疗更强。RNAseq分析显示lncRNA HOTTIP在Exo血清中显著上调。此外，lncRNA HOTTIP敲低逆转了Exo-MP（TAF）对HepAD 38细胞的抗病毒作用，而lncRNA HOTTIP敲低发挥了相反的作用。总之，这些结果表明，外泌体lncRNA HOTTIP是必不可少的TAF的抗病毒活性，并提供了一个新的理解外泌体介导的机制，HBV感染。
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. 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)). 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. 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.