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Deoxycholic acid liganded HBs contributes to HBV maturation

Gao, Y.; Ning, Q.; Yang, P.; Zhang, Y.; Guan, Y.; Liu, N.; Ben, H.; Wang, Y.; Liu, M.; Yang, T.; Cai, Y.; Hu, Z.; Jiang, M.; Chen, D.

2021-12-30 infectious diseases
10.1101/2021.12.21.21268182 medRxiv
Show abstract

Understanding the underlying mechanism of HBV maturation and subviral particle production is critical to control HBV infection and develop new antiviral strategies. Here, we demonstrate that deoxycholic acid (DCA) plays a central role in HBV production. HBV infection increased DCA levels, whereas elimination of DCA-producing microbiome decreased HBV viral load. DCA can bind to HBs antigen via LXXLL motif at TM1 and TM2 region to regulate HBs-HBc interaction and the production of mature HBV. Plasma DCA levels from patients undergoing antiviral therapy were significantly higher in those with positive HBV viral load. These results suggest that intestinal DCA-producing microbiome can affect the efficiency of antiviral therapy and provide a potential novel strategy for HBV antiviral therapy. One Sentence SummaryWe demonstrate that DCA-promoted HBs-HBc interaction and contributes to HBV maturation.

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