Persistence of the recombinant genomes of woodchuck hepatitis virus in the mouse model.
Hydrodynamic injection (HI) with a replication competent hepatitis B virus (HBV) genome may lead to transient or prolonged HBV replication in mice. However, the prolonged HBV persistence after HI depends on the specific backbone of the vector carrying HBV genome and the genetic background of the mouse strain. We asked whether a genetically closely related hepadnavirus, woodchuck hepatitis virus (WHV), may maintain the gene expression and replication in the mouse liver after HI. Interestingly, we found that HI of pBS-WHV1.3 containing a 1.3 fold overlength WHV genome in BALB/c mouse led to the long presence of WHV DNA and WHV proteins expression in the mouse liver. Thus, we asked whether WHV genome carrying foreign DNA sequences could maintain the long term gene expression and persistence. For this purpose, the coding region of HBV surface antigen (HBsAg) was inserted into the WHV genome to replace the corresponding region. Three recombinant WHV-HBV genomes were constructed with the replacement with HBsAg a-determinant, major HBsAg, and middle HBsAg. Serum HBsAg, viral DNA, hepatic WHV protein expression, and viral replication intermediates were detected in mice after HI with recombinant genomes. Similarly, the recombinant genomes could persist for a prolonged period of time up to 45 weeks in mice. WHV and recombinant WHV-HBV genomes did not trigger effective antibody and T-cell responses to viral proteins. The ability of recombinant WHV constructs to persist in mice is an interesting aspect for the future investigation and may be explored for in vivo gene transfer.
Department of Microbiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Danzhen
D
Pan
Department of Microbiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yong
Y
Lin
Department of Microbiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Weimin
W
Wu
Division of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jingjiao
J
Song
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Ejuan
E
Zhang
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Chunchen
C
Wu
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Xinwen
X
Chen
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Kanghong
K
Hu
Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Dongliang
D
Yang
Department of Microbiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yang
Y
Xu
Department of Microbiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Virology, University Hospital of Essen, Essen, Germany.
Mengji
M
Lu
D000818:Animals; D004279:DNA, Viral; D004195:Disease Models, Animal; D005260:Female; D023061:Gene Order; D005822:Genetic Vectors / Q000235:genetics; D016679:Genome, Viral; D006509:Hepatitis B / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics* / Q000276:immunology; D016130:Immunophenotyping; D008099:Liver / Q000378:metabolism / Q000821:virology; D051379:Mice; D016865:Reassortant Viruses; D011995:Recombination, Genetic; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D014764:Viral Proteins