Masaya Sugiyama and Yasuhito Tanaka contributed equally to this study.
Early dynamics of hepatitis B virus in chimeric mice carrying human hepatocytes monoinfected or coinfected with genotype G†
Article first published online: 28 MAR 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 45, Issue 4, pages 929–937, April 2007
How to Cite
Sugiyama, M., Tanaka, Y., Sakamoto, T., Maruyama, I., Shimada, T., Takahashi, S., Shirai, T., Kato, H., Nagao, M., Miyakawa, Y. and Mizokami, M. (2007), Early dynamics of hepatitis B virus in chimeric mice carrying human hepatocytes monoinfected or coinfected with genotype G. Hepatology, 45: 929–937. doi: 10.1002/hep.21584
Potential conflict of interest: Nothing to report.
- Issue published online: 28 MAR 2007
- Article first published online: 28 MAR 2007
- Manuscript Accepted: 1 DEC 2006
- Manuscript Received: 12 AUG 2006
- Ministry of Health, Labor, and Welfare of Japan. Grant Number: H16-kanen-3
- Scientific Research from the Ministry of Education. Grant Number: 18590741
- Toyoaki Foundation
Of the 8 genotypes of HBV (genotypes A-H), genotype G is unique in that it has an insertion in the core gene and two stop codons in the precore region preventing the synthesis of hepatitis B e antigen. Most individuals with genotype G are coinfected with other genotypes, typically genotype A. Mice with severe combined immunodeficiency disease carrying human hepatocytes were infected with HBV particles propagated in Huh7 cells in culture. Mice monoinfected with genotype G did not raise detectable HBV DNA in serum, although products of the core gene emerged 4 to 8 weeks after inoculation. When they were superinfected with genotype A at week 10, however, HBV DNA of genotype A developed, which was replaced almost completely by that of genotype G within 10 weeks. Such a rapid takeover was also observed in mice initially infected with genotype A or C and superinfected with genotype G. Similar viral dynamics occurred in mice simultaneously coinfected with genotypes G and A. Takeover was markedly enhanced in mice inoculated with a serum passage containing genotype G with a trace of genotype A. Coinfection of mice with genotypes G and A induced abundant cellular steatosis along with increased fibrosis in the liver, which was not detected in mice monoinfected with genotype A or G. Conclusion: Genotype G can monoinfect chimeric mice at very low levels, and its replication increases maredly when coinfected with other genotypes. Coinfection with genotype G could enhance fibrosis under immunocompromised states. (HEPATOLOGY 2007;45:929–937.)