Antiviral Activity of Bay 41-4109 on Hepatitis B Virus in Humanized Alb-uPA/SCID Mice

Brezillon, Nicolas; Brunelle, Marie-Noëlle; Massinet, Hé lène; Giang, Eric; Lamant, Cé line; DaSilva, Lucie; Berissi, Sophie; Belghiti, Jacques; Hannoun, Laurent; Puerstinger, Gherard; Wimmer, Eva; Neyts, Johan; Hantz, Olivier; Soussan, Patrick; Morosan, Serban; Kremsdorf, Dina
December 2011
PLoS ONE;2011, Vol. 6 Issue 12, p1
Academic Journal
Current treatments for HBV chronic carriers using interferon alpha or nucleoside analogues are not effective in all patients and may induce the emergence of HBV resistant strains. Bay 41-4109, a member of the heteroaryldihydropyrimidine family, inhibits HBV replication by destabilizing capsid assembly. The aim of this study was to determine the antiviral effect of Bay 41-4109 in a mouse model with humanized liver and the spread of active HBV. Antiviral assays of Bay 41-4109 on HepG2.2.15 cells constitutively expressing HBV, displayed an IC50 of about 202 nM with no cell toxicity. Alb-uPA/SCID mice were transplanted with human hepatocytes and infected with HBV. Ten days post-infection, the mice were treated with Bay 41-4109 for five days. During the 30 days of follow-up, the HBV load was evaluated by quantitative PCR. At the end of treatment, decreased HBV viremia of about 1 log(10) copies/ml was observed. By contrast, increased HBV viremia of about 0.5 log(10) copies/ml was measured in the control group. Five days after the end of treatment, a rebound of HBV viremia occurred in the treated group. Furthermore, 15 days after treatment discontinuation, a similar expression of the viral capsid was evidenced in liver biopsies. Our findings demonstrate that Bay 41-4109 displayed antiviral properties against HBV in humanized Alb-uPA/SCID mice and confirm the usefulness of Alb-uPA/SCID mice for the evaluation of pharmaceutical compounds. The administration of Bay 41-4109 may constitute a new strategy for the treatment of patients in escape from standard antiviral therapy.


Related Articles

  • Hepatitis B viraemia: its heritability and association with common genetic variation in the interferon γ signalling pathway. Hsuan-Hao Huang // Gut;Jan2011, Vol. 60 Issue 1, p99 

    OBJECTIVE: High viraemia of hepatitis B virus (HBV) influences all phases in the development of hepatocellular carcinoma (HCC). This study was designed to estimate the overall contribution of host genetics to HBV viraemia, and investigate the influence of common single-nucleotide polymorphisms...

  • AASLD Updates Chronic Hepatitis B Recommendations. HUNTZINGER, AMBER // American Family Physician;2/15/2009, Vol. 79 Issue 4, p338 

    The article focuses on the updated chronic hepatitis B virus (HBV) infection recommendations from the American Association for the Study of Liver Diseases (AASLD), which include the preferred diagnostic, therapeutic, and preventive approaches to chronic HBV. It notes that chronic HBV infection...

  • Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis. Wong, David K.H.; Cheung, Angela M.; O'Rourke, Keith; Naylor, C. David; Detsky, Allan S.; Heathcote, Jenny; Wong, D K; Cheung, A M; O'Rourke, K; Naylor, C D; Detsky, A S; Heathcote, J // Annals of Internal Medicine;8/15/93, Vol. 119 Issue 4, p312 

    Purpose: To determine whether alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic hepatitis B virus (HBV) infection.Data Sources: Randomized controlled studies published in the English literature...

  • Genotype Mixtures of Hepatitis B Virus in Patients Treated with Interferon. Hannoun, Charles; Krogsgaard, Kim; Horal, Petr; Lindh, Magnus // Journal of Infectious Diseases;9/15/2002, Vol. 186 Issue 6, p752 

    Little is known about coinfection among several hepatitis B virus (HBV) genotypes, although previous reports of recombination and genotype shifts indicate that this should occur. In the present study, we designed a method to identify mixtures of genotype A and another genotype, regardless of...

  • Effective Inhibition of HBV Replication in Vivo by Anti-HBx Short Hairpin RNAs. Carmona, Sergio; Ely, Abdullah; Crowther, Carol; Moolla, Naazneen; Salazar, Felix H.; Marion, Patricia L.; Ferry, Nicolas; Weinberg, Marc S.; Arbuthnot, Patrick // Molecular Therapy;Feb2006, Vol. 13 Issue 2, p411 

    Exploiting the RNA interference pathway has shown promise for developing novel and effective treatment of hepatitis B virus (HBV) infection. To advance this approach, we analyzed the antiviral efficacy of a panel of 10 Pol III U6 promoter-encoded short hairpin RNAs (shRNAs) that target conserved...

  • Identification of BST-2/tetherin-induced hepatitis B virus restriction and hepatocyte-specific BST-2 inactivation. Lv, Mingyu; Zhang, Biao; Shi, Ying; Han, Zhu; Zhang, Yan; Zhou, Yulai; Zhang, Wenyan; Niu, Junqi; Yu, Xiao-Fang // Scientific Reports;7/3/2015, p11736 

    BST-2/tetherin is an interferon-inducible antiviral protein that blocks the release of various enveloped viruses, including HIV-1. Hepatitis B virus (HBV), a major cause of liver disease, belongs to the Hepadnaviridae family of enveloped DNA viruses. Whether BST-2 regulates HBV production is...

  • Exosomes mediate the cell-to-cell transmission of IFN-α-induced antiviral activity. Li, Jianhua; Liu, Kuancheng; Liu, Yang; Xu, Yan; Zhang, Fei; Yang, Huijuan; Liu, Jiangxia; Pan, Tingting; Chen, Jieliang; Wu, Min; Zhou, Xiaohui; Yuan, Zhenghong // Nature Immunology;Aug2013, Vol. 14 Issue 8, p793 

    The cell-to-cell transmission of viral resistance is a potential mechanism for amplifying the interferon-induced antiviral response. In this study, we report that interferon-α (IFN-α) induced the transfer of resistance to hepatitis B virus (HBV) from nonpermissive liver nonparenchymal...

  • Adding interferon to lamivudine enhances the early virologic response and reversion of the precore mutation in difficult-to-treat HBV infection. Yuki, Nobukazu; Nagaoka, Takayuki; Nukui, Kazuhiko; Omura, Masao; Hikiji, Kazumasa; Kato, Michio // Journal of Gastroenterology;2008, Vol. 43 Issue 6, p457 

    The virologic impact of adding interferon to antiviral nucleoside therapy was studied in Japanese patients having perinatally transmitted hepatitis B virus (HBV) genotype C. Sixty-four patients including 41 positive for hepatitis B e antigen (HBeAg) were assigned to receive either (1) a...

  • 2008 - Review: Interferon and nucleoside/tide analogues reduce risk for hepatocellular cancer in patients with chronic hepatitis B. Sherker, Averell H. // ACP Journal Club;4/21/2009, Vol. 150 Issue 4, p9 

    The article discusses, studies which tried to find out whether interferon and nucleoside/tide analogues reduce risk for hepatocellular cancer (HCC) in patients with chronic hepatitis B virus (HBV) infection. The meta-analysis conformed that interferon and nucleoside/tide analogues reduces risk...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics