Successful establishment and evaluation of a new animal model for studying the hepatitis B virus YVDD mutant

Successful establishment and evaluation of a new animal model for studying the hepatitis B virus... The treatment of infection with lamivudine-resistant mutants of hepatitis B virus (HBV) with mutations in the YMDD motif has become a crucial issue in the clinic. In this work, the plasmids pcDNA3.1 (+)-HBV/C-YVDD and pcDNA3.1 (+)-HBV/C-YMDD were constructed and injected into BALB/c mice using a hydrodynamics-based procedure to investigate viral replication and expression of HBV lamivudine-resistant YVDD mutants in vivo . Compared with the YMDD group, HBsAg levels were higher in sera of mice in the YVDD group, but HBeAg levels were lower on day 1 after injection. Levels of HBcAg in hepatocytes were higher in the YVDD group on day 1, whereas the HBsAg levels were lower. The levels of HBV mRNA in the liver were higher in mice in the YVDD group on day 1 after injection. The results showed that injection with these plasmids resulted in efficient initiation of replication of HBV in mice and also suggested that the combined mutations in YVDD mutants could affect the replication process. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Successful establishment and evaluation of a new animal model for studying the hepatitis B virus YVDD mutant

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Publisher
Springer Vienna
Copyright
Copyright © 2013 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-012-1550-1
Publisher site
See Article on Publisher Site

Abstract

The treatment of infection with lamivudine-resistant mutants of hepatitis B virus (HBV) with mutations in the YMDD motif has become a crucial issue in the clinic. In this work, the plasmids pcDNA3.1 (+)-HBV/C-YVDD and pcDNA3.1 (+)-HBV/C-YMDD were constructed and injected into BALB/c mice using a hydrodynamics-based procedure to investigate viral replication and expression of HBV lamivudine-resistant YVDD mutants in vivo . Compared with the YMDD group, HBsAg levels were higher in sera of mice in the YVDD group, but HBeAg levels were lower on day 1 after injection. Levels of HBcAg in hepatocytes were higher in the YVDD group on day 1, whereas the HBsAg levels were lower. The levels of HBV mRNA in the liver were higher in mice in the YVDD group on day 1 after injection. The results showed that injection with these plasmids resulted in efficient initiation of replication of HBV in mice and also suggested that the combined mutations in YVDD mutants could affect the replication process.

Journal

Archives of VirologySpringer Journals

Published: Apr 1, 2013

References

  • Hepatitis B infection: current concepts and future challenges
    Nebbia, G; Peppa, D; Maini, MK
  • Prevalence and clinical characterization of patients with acute hepatitis B induced by lamivudine-resistant strains
    Hayashi, K; Katano, Y; Ishigami, M; Itoh, A; Hirooka, Y; Nakano, I; Yoshioka, K; Yano, M; Toyoda, H; Kumada, T; Goto, H
  • Nucleoside/nucleotide analogues in the treatment of chronic hepatitis B
    Fung, J; Lai, CL; Seto, WK; Yuen, MF
  • Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation
    Lutgehetmann, M; Mancke, LV; Volz, T; Helbig, M; Allweiss, L; Bornscheuer, T; Pollok, JM; Lohse, AW; Petersen, J; Urban, S; Dandri, M

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