Immunosuppressive drugs modulate the replication of hepatitis B virus (HBV) in a hydrodynamic injection mouse model.
Hepatitis B virus (HBV) reactivation and recurrence are common in patients under immunosuppression and can be controlled by hepatitis B immunoglobulin, antivirals, and hepatitis B vaccine. However, the detailed analysis of HBV infection under immunosuppression is essential for the prophylaxis and therapy for HBV reactivation and recurrence. In this study, HBV replication and T cell responses were analyzed in a HBV-transfected mouse model under immunosuppressive therapy. During the treatment, HBV replication was at a high level in mice treated with dexamethasone, cyclosporine, and cyclophosphamide, whereas was terminated in mice treated with mycophenolate mofetil. After the withdrawal, HBV replication was at low or high levels in the dexamethasone-treated mice or in both cyclosporine- and cyclophosphamide-treated mice. The early withdrawal of cyclosporine allowed the recovery of suppressed T cell responses and led to subsequent HBV clearance, while the adoptive immune transfer to the mice with HBV persistence led to HBV suppression. Taken together, long-term HBV persistence under immunosuppression depends on the immunosuppressive drugs used and on the treatment duration and is mediated by the suppressed intrahepatic CD8 T cell response. These data may be helpful for individualized immunosuppressive therapy in patients with high risk of HBV reactivation and recurrence, and the mouse system is suitable for studying HBV reactivation and recurrence under immunosuppression.
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Junzhong
J
Wang
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Baoju
B
Wang
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Shunmei
S
Huang
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhitao
Z
Song
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jun
J
Wu
Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ejuan
E
Zhang
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Zhenni
Z
Zhu
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Bin
B
Zhu
Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ying
Y
Yin
Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yong
Y
Lin
Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yang
Y
Xu
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xin
X
Zheng
Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Germany.
Mengji
M
Lu
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Dongliang
D
Yang
D019264:Adoptive Transfer; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006509:Hepatitis B / Q000276:immunology / Q000821:virology*; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology*; D057446:Hydrodynamics; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007267:Injections; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects*
D007166:Immunosuppressive Agents; D016572:Cyclosporine