Utilization of transgenic mice replicating high levels of hepatitis B virus for antiviral evaluation of lamivudine.
A recently developed transgenic mouse strain which expresses high levels of hepatitis B virus (HBV) was studied as a model for evaluation of potential chemotherapeutic agents. Lamivudine ([-]2'-deoxy-3'-thiacytidine), known to reduce hepatitis B viremia in human patients, and zidovudine (3'-azido-3'-deoxythymidine), previously shown to be ineffective for HBV infections in man, were used in parallel in this transgenic animal model. Orally administered lamivudine at dosages of 100, 50, and 25 mg/kg per day given once a day for 21 days significantly decreased serum and liver HBV DNA titers in a dose-responsive manner. Zidovudine (approximately 22 mg/kg per day) administered in the drinking water for 21 days was not effective in reducing these HBV parameters as compared to transgenic placebo-treated controls. The serum HBV DNA titers rebounded to high levels 1 week after cessation of lamivudine treatment. Male and female mice responded in a similar manner to these therapies. The results using this transgenic mouse model were similar to what would be predicted from treatment of HBV-infected human patients with lamivudine and zidovudine, and indicate these mice may be useful as a small animal chemotherapeutic model for study of potential HBV inhibitors.
Morrey
J D
JD
Institute for Antiviral Research, Utah State University, Logan 84322-5600, USA. jmorrey@cc.usu.edu
Bailey
K W
KW
Korba
B E
BE
Sidwell
R W
RW
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000187:drug effects; D006513:Hepatitis B e Antigens / Q000097:blood / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013997:Time Factors; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000627:therapeutic use
D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D019259:Lamivudine; D015215:Zidovudine