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

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

J Inflamm Res

Infection Control Center, Linyi People's Hospital, Linyi, Shandong Province, People's Republic of China.

Published: October 2021

AI Article Synopsis

  • Chronic hepatitis B (CHB) affects about 292 million people worldwide, and Tenofovir alafenamide (TAF) is a key treatment, although its exact antiviral mechanism isn't fully understood.
  • The study explored the antiviral effects of exosomes from serum of CHB patients treated with TAF and TAF-treated macrophages on HepAD38 cells, finding they significantly reduced HBV levels more effectively than TAF alone.
  • RNA sequencing revealed that lncRNA HOTTIP was notably upregulated in the exosomes, and knocking it down reversed the antiviral effects, indicating its essential role in TAF's antiviral activity against HBV.

Article Abstract

Introduction: 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550561PMC
http://dx.doi.org/10.2147/JIR.S315716DOI Listing

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