%0 Journal Article
%T Paclitaxel-induced Immune Dysfunction and Activation of Transcription Factor AP-1 Facilitate Hepatitis B Virus Replication.
%A Chen S
%A Li B
%A Luo W
%A Rehman AU
%A He M
%A Yang Q
%A Wang S
%A Guo J
%A Chen L
%A Li X
%J J Clin Transl Hepatol
%V 12
%N 5
%D 2024 May 28
%M 38779518
%F 5.065
%R 10.14218/JCTH.2023.00537
%X <B>UNASSIGNED: </B>Hepatitis B virus (HBV) reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy. Paclitaxel (PTX) treatment has been identified as a potential trigger for HBV reactivation. This study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo, which may inform new strategies for HBV antiviral treatment.<BR><B>UNASSIGNED: </B>The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay, dual-luciferase reporter assay, quantitative real-time PCR, chromatin immunoprecipitation, and immunohistochemical staining. Transcriptome sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic mice.<BR><B>UNASSIGNED: </B>PTX enhanced the levels of HBV 3.5-kb mRNA, HBV DNA, HBeAg, and HBsAg both in vitro and in vivo. PTX also promoted the activity of the HBV core promoter and transcription factor AP-1. Inhibition of AP-1 gene expression markedly suppressed PTX-induced HBV reactivation. Transcriptome sequencing revealed that PTX activated the immune-related signaling networks such as IL-17, NF-κB, and MAPK signaling pathways, with the pivotal common key molecule being AP-1. The 16S rRNA sequencing revealed that PTX induced dysbiosis of gut microbiota.<BR><B>UNASSIGNED: </B>PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor AP-1. These findings propose a novel molecular mechanism, underscoring the critical role of AP-1 in PTX-induced HBV reactivation.