Peroxisome Proliferators Activated Receptor (PPAR) agonists activate hepatitis B virus replication in vivo

Abstract

BackgroundPPAR agonists are often used in HBV infected patients with metabolic disorders. However, as liver-enriched transcriptional factors, PPARs would activate HBV replication. Risks exsit in such patients. This study aimed to assess the influence of commonly used synthetic PPAR agonists on hepatitis B virus (HBV) transcription, replication and expression through HBV replicative mouse models, providing information for physicians to make necessary monitoring and therapeutic adjustment when HBV infected patients receive PPAR agonists treatment.MethodsThe HBV replicative mouse model was established by hydrodynamic injection of HBV replicative plasmid and the mice were divided into four groups and treated daily for 3 days with saline, PPAR pan-agonist (bezafibrate), PPARα agonist (fenofibrate) and PPARγ agonist (rosiglitazone) respectively. Their serum samples were collected for ECLIA analysis of HBsAg and HBeAg and real-time PCR analysis of Serum HBV DNA. The liver samples were collected for DNA (Southern) filter hybridization of HBV replication intermediates, real-time PCR analysis of HBV mRNA and immunohistochemistry (IHC) analysis of hepatic HBcAg. The alternation of viral transcription, replication and expression were compared in these groups.ResultSerum HBsAg, HBeAg and HBV DNA were significantly elevated after PPAR agonist treatment. So did the viral replication intermediates in mouse livers. HBV mRNA was also significantly increased by these PPAR agonists, implying that PPAR agonists activate HBV replication at transcription level. Moreover, hepatic HBcAg expression in mouse livers with PPAR agonist treatment was elevated as well.ConclusionOur in vivo study proved that synthetic PPAR agonists bezafibrate, fenofibrate and rosiglitazone would increase HBV replication. It suggested that when HBV infected patients were treated with PPARs agonists because of metabolic diseases, HBV viral load should be monitored and regimens may need to be adjusted, an antiviral therapy may be added.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-017-0765-x) contains supplementary material, which is available to authorized users.

Increased expression of phosphoenolpyruvate carboxykinase cytoplasmic isoform by hepatitis B virus X protein affects hepatitis B virus replication

“…PPAR‐γ belongs to the nuclear hormone receptor superfamily and is coactivated by PGC‐1α . Our group has recently demonstrated that rosiglitazone, a PPAR‐γ agonist, is able to activate HBV transcription and replication in a hydrodynamic HBV replicative mouse model . This corroborates a previous study showing the dual inhibition of PGC‐1α and PPAR‐γ simultaneously strongly inhibits HBV replication .…”

Can Echinacea be a potential candidate to target immunity, inflammation, and infection - The trinity of coronavirus disease 2019

“…Additionally, PPARγ agonists have been shown to inhibit the replication of numerous viruses including HIV, RSV, hepatitis B, and hepatitis C [ 103 , 104 ]. Furthermore, PPARγ agonists have been shown to reduce morbidity and mortality in infections with influenza A virus [ 105 ].…”

Circadian control of hepatitis B virus replication

“…Lipid and bile acid metabolism are circadian regulated including the expression of transcription factors, peroxisome proliferator-activated receptor and sterol regulatory element-binding protein (reviewed in ref. 25 ) that have been reported to activate HBV transcription [26][27][28] . The liver-specific transcription factor HNF4α has been linked to HBV tropism 29 and interacts with circadian components BMAL1/CLOCK 30 and REV-ERB 31 .…”