Peroxisome Proliferators Activated Receptor (PPAR) agonists activate hepatitis B virus replication in vivo
Abstract Background PPAR 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 agonist...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2017-05-01
|
Series: | Virology Journal |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12985-017-0765-x |
id |
doaj-0b20e45ba0f6450c830d464dd8f2e9fa |
---|---|
record_format |
Article |
spelling |
doaj-0b20e45ba0f6450c830d464dd8f2e9fa2020-11-25T00:44:56ZengBMCVirology Journal1743-422X2017-05-011411910.1186/s12985-017-0765-xPeroxisome Proliferators Activated Receptor (PPAR) agonists activate hepatitis B virus replication in vivoLingyao Du0Yuanji Ma1Miao Liu2Libo Yan3Hong Tang4Center of Infectious Diseases, West China Hospital of Sichuan UniversityCenter of Infectious Diseases, West China Hospital of Sichuan UniversityCenter of Infectious Diseases, West China Hospital of Sichuan UniversityCenter of Infectious Diseases, West China Hospital of Sichuan UniversityCenter of Infectious Diseases, West China Hospital of Sichuan UniversityAbstract Background PPAR 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. Methods The 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. Result Serum 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. Conclusion Our 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.http://link.springer.com/article/10.1186/s12985-017-0765-xPPARAgonistHBVReplication |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lingyao Du Yuanji Ma Miao Liu Libo Yan Hong Tang |
spellingShingle |
Lingyao Du Yuanji Ma Miao Liu Libo Yan Hong Tang Peroxisome Proliferators Activated Receptor (PPAR) agonists activate hepatitis B virus replication in vivo Virology Journal PPAR Agonist HBV Replication |
author_facet |
Lingyao Du Yuanji Ma Miao Liu Libo Yan Hong Tang |
author_sort |
Lingyao Du |
title |
Peroxisome Proliferators Activated Receptor (PPAR) agonists activate hepatitis B virus replication in vivo |
title_short |
Peroxisome Proliferators Activated Receptor (PPAR) agonists activate hepatitis B virus replication in vivo |
title_full |
Peroxisome Proliferators Activated Receptor (PPAR) agonists activate hepatitis B virus replication in vivo |
title_fullStr |
Peroxisome Proliferators Activated Receptor (PPAR) agonists activate hepatitis B virus replication in vivo |
title_full_unstemmed |
Peroxisome Proliferators Activated Receptor (PPAR) agonists activate hepatitis B virus replication in vivo |
title_sort |
peroxisome proliferators activated receptor (ppar) agonists activate hepatitis b virus replication in vivo |
publisher |
BMC |
series |
Virology Journal |
issn |
1743-422X |
publishDate |
2017-05-01 |
description |
Abstract Background PPAR 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. Methods The 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. Result Serum 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. Conclusion Our 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. |
topic |
PPAR Agonist HBV Replication |
url |
http://link.springer.com/article/10.1186/s12985-017-0765-x |
work_keys_str_mv |
AT lingyaodu peroxisomeproliferatorsactivatedreceptorpparagonistsactivatehepatitisbvirusreplicationinvivo AT yuanjima peroxisomeproliferatorsactivatedreceptorpparagonistsactivatehepatitisbvirusreplicationinvivo AT miaoliu peroxisomeproliferatorsactivatedreceptorpparagonistsactivatehepatitisbvirusreplicationinvivo AT liboyan peroxisomeproliferatorsactivatedreceptorpparagonistsactivatehepatitisbvirusreplicationinvivo AT hongtang peroxisomeproliferatorsactivatedreceptorpparagonistsactivatehepatitisbvirusreplicationinvivo |
_version_ |
1725272419237625856 |