Functional Characterization of Interferon Regulation Element of Hepatitis B virus Genome In Vivo

Liu, Fengjun; Chen, En‐Qiang; Zhou, Qiaoling; Zhou, Tong; Liu, Cong; Liu, Li; Xing, Cheng; Tang, Hong

doi:10.1007/s13337-012-0091-2

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…Therefore, these results indicate that the mutations in the HBV RT region may reduce the inhibitory effect of IFN-α on HBV replication. Furthermore, the IFN regulatory element mutant in HBV genome reduced the inhibitory effect of IFN-α on HBV replication in our mouse model of HBV replication (Motta et al, 2010;Liu et al, 2012). During IFN-α treatment, multiple mutations occurred in the HBV genome, including the viral polymerase, precore, core and the core promoter regions (Chen et al, 2003).…”

Section: Discussionmentioning

confidence: 73%

Sensitivity of drug-resistant mutants of hepatitis B virus to poly-IC

Zhou¹,

Chen²,

Chen³

et al. 2014

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Summary. -The long-term benefits of antiviral treatment are limited by the resistance of hepatitis B virus (HBV). However, the effect of interferon (IFN)α treatment on drug-resistant HBVs is so far unknown. We, therefore, investigated the effects of IFN-α inducer poly-IC on the replication of HBV mutants resistant to drugs such as lamivudine (LAM), adefovir dipivoxil (ADV) and entecavir (ETV) in mice. HBV DNA and HBV DNA intermediate (RI) were employed as markers of the virus replication and 2',5'-oligoadenylate synthase (OAS) mRNA as a marker of IFN-α/β induction. Poly-IC inhibited wtHBV replication and increased levels of OAS mRNA. Compared to the wt virus, the capacity of virus replication was reduced in most LAMr and ETVr mutants except those with mutations rtM(204V+L180M+V173L), and was similary in the ADVr mutants except rt(A121V+N236T). The virus replication was reduced after poly-IC treatment with LAMr and ADVr mutants similary to the wt virus. In contrast, ETVr mutants were resistant to the poly-IC treatment. In conclusion, the capacity of HBV replication and the sensitivity to IFN therapy are influenced by drug-resistant mutations. The IFN therapy may effectively inhibit HBV replication in particular in patients with LAMr or ADVr mutations but not in patients with ETVr mutations.Keywords: hepatitis B virus; mutants; drugs; mouse; interferon; poly-IC * Corresponding author. E-mail: htang6198@hotmail.com; phone: +86-28-8542-2650. Abbreviations: ADV = adefovir dipivoxil; ETV = entecavir; HBV = hepatitis B virus; HBeAg = hepatitis B envelope antigen; HCC = hepatocellular carcinoma; IFN = interferon; LAM = lamivudine; LdT = telbivudine; OAS = 2', 5'-oligoadenylate synthase; r = resistant; RI = replication intermediates; rt,RT = reverse transcriptase; TDF = tenofovir disoproxil fumarate

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Section: Discussionmentioning

confidence: 73%

Sensitivity of drug-resistant mutants of hepatitis B virus to poly-IC

Zhou¹,

Chen²,

Chen³

et al. 2014

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“…For simulating an in vivo environment with relative high ZAP expression and HBV replication, HBV expression plasmid pHBV4.1 was subsquently delivered to this ZAP transgenic mouse liver via tail vein injection. Previous study had found that the HBV DNA replication intermediates in this mouse model were abundant on day 3 and 4, and disappeared on day 10 [ 29 ], thus day 3 after transfection was a widely used timepoint to evaluate the change of HBV transcription and replication levels [ 30 , 31 ]. Based on the previous research experience, the role of host ZAP against HBV transcription and replication in present study was also evaluated at this timepoint.…”

Section: Discussionmentioning

confidence: 99%

The efficacy of zinc finger antiviral protein against hepatitis B virus transcription and replication in tansgenic mouse model

Chen

Dai

Bai

et al. 2015

Virol J

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AimThe zinc finger antiviral protein (ZAP) is a mammalian host restriction factor, and it could inhibit HBV RNA synthesis in vitro experiments. However, the role of ZAP against HBV in vivo environment is unclear. This study aimed to investigate whether ZAP could act against HBV transcription and replication in ZAP tansgenic mouse model.MethodsHBV-replication-competent plasmid pHBV4.1 was transferred to ZAP transgenic ICR mouse via the tail vein using a hydrodynamic in vivo transfection procedure, and ICR mouse were used as controls. HBV RNA and HBV DNA replication intermediates in the liver were respectively analyzed by Northern blotting and Southern blotting. The expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in the liver tissue was detected by immunohistochemical staining.ResultsAs compared to ICR control mouse, the levels of 3.5 kb mRNA in ZAP transgenic mouse were decreased by 8.4%; while the level of HBV DNA replication intermediates was decreased by 82%. In addition, the expression of HBsAg and HBcAg in ZAP transgenic mouse liver were both significantly less than that of ICR control mouse.ConclusionsOur findings suggest that ZAP could inhibit HBV replication in vivo in mice, which offers a new target for anti-HBV drug development.

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“…Related reports of using these methods demonstrate that modified silicone rubber can show better mechanical damping properties. Through the blend of hydroxyl-terminated polybutadiene [4] and polysiloxane, organic silicon and acrylates [5], silicone rubber and cis-polybutadiene rubber/ethylene-propylene-diene [6], polyurethane elastom and phenyl silicone rubber [7], polymethylvinylsiloxane and butyl rubber [8], the modified silicone rubbers had improved damping properties on a wide temperature range. By adding Reinforcing filler SiO 2 to methyl-phenyl-vinyl silicone rubber and comparing the damping and vibration isolation properties of three different rubbers, a high vibration-damping mechanism had been obtained [9].…”

Section: Introductionmentioning

confidence: 99%

Mechanical Damping Properties of Silicone Rubber Prepared by Nano-SiO<sub>2</sub> and AGE-Modified Polysiloxane Blends

Cai

Zhang

et al. 2011

AMR

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The synthesis of AGE modified polysiloxane was realized by block copolymerization. Using degradation method and different ratio of raw materials, different content of AGE side chains and molecular weight of AGE modified polysiloxanes had been obtained. AGE modified silicone rubber was prepared by Nano-SiO2and AGE-Modified Polysiloxane Blends. The relationship between the molecular weight of AGE modified polysiloxane, the content of AGE modified side chains and the mechanical properties of AGE modified silicone rubber had been studied. The results showed that AGE modified silicone rubber had better mechanical damping properties than silicone rubber without modification of AGE: lower Tg (-56°C), higher tanδ (0.26), the maximum tensile/rear strengths with appropriate dynamic viscosity (17500mP•s) and the characterization of decreasing tensile/tear strengths with the increasing content of the AGE modified side chains.

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Functional Characterization of Interferon Regulation Element of Hepatitis B virus Genome In Vivo

Cited by 4 publications

References 36 publications

Sensitivity of drug-resistant mutants of hepatitis B virus to poly-IC

Sensitivity of drug-resistant mutants of hepatitis B virus to poly-IC

The efficacy of zinc finger antiviral protein against hepatitis B virus transcription and replication in tansgenic mouse model

Mechanical Damping Properties of Silicone Rubber Prepared by Nano-SiO<sub>2</sub> and AGE-Modified Polysiloxane Blends

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