Enhanced duck hepatitis B virus gene expression following aflatoxin B1 exposure

被引:24
作者
Barraud, L
Guerret, S
Chevallier, M
Borel, C
Jamard, C
Trepo, C
Wild, CP
Cova, L
机构
[1] INSERM, U271, F-69424 Lyon 03, France
[2] Labs Marcel Mecieux, Lyon, France
[3] Univ Leeds, Sch Med, Mol Epidemiol Unit, Leeds LS2 9JT, W Yorkshire, England
关键词
D O I
10.1002/hep.510290441
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Epidemiological studies have suggested synergistic interactions between chronic hepatitis B virus (HBV) infection and aflatoxin B-1 (AFB(1)) exposure in the etiology of hepatocellular carcinoma (HCC), although the molecular mechanisms of their interactions are still not understood. The aim of this study was to use the Pekin duck model to investigate the impact of AFB(1) exposure on duck hepatitis B virus (DHBV) replication during the early stages of virus-carcinogen interactions. Six-week-old chronic DHBV-carrier or uninfected ducks were exposed to AFB(1) for 5 weeks or treated with dimethylsulfoxide (DMSO) as a control. Animals were observed for 6 to 13 weeks after AFB(1) treatment to study the influence of AFB(1) exposure on DHBV replication and liver pathologies. Histological analysis showed more marked changes in the livers of AFB(1)-treated ducks, and these were enhanced by DHBV infection. A significant increase in serum and liver DHBV DNA level was observed in AFB(1)-treated ducks as compared with DMSO-treated controls. In addition, viral RNAs, in particular the pregenomic RNA. that is the template of viral replication, and intrahepatic DHBV DNA replicative intermediates, were significantly increased by AFB(1) treatment. Moreover, an overexpression and accumulation of DHBV large envelope (L) protein was observed in the hepatocytes of AFB(1)-exposed animals. The in vitro study has further confirmed an increase in intracellular viral DNA and in virus release in AFB(1)-treated primary duck hepatocytes. Taken together, our results indicate that AFB(1) exposure leads to an increase in virus gene expression associated with intrahepatic accumulation of DHBV L protein and enhanced liver pathology.
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页码:1317 / 1323
页数:7
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