Immunosuppression reactivates viral replication long after resolution of woodchuck hepatitis virus infection.
Resolution of hepatitis B virus (HBV) infection is characterized by coordinated humoral and cellular immune responses. Immunity is durable over decades, protecting the host from reinfection and potential activation of residual HBV. Woodchucks infected at birth with woodchuck hepatitis virus (WHV) cleared viremia and developed antibodies to surface antigen (anti-WHs). Woodchucks became seronegative for anti-WHs 3-6 years later, but in some, WHV DNA was detected in serum, liver, and/or peripheral blood mononuclear cells (PBMCs). Those with WHV DNA had increased in vitro cellular immune responses to viral antigens, CD4 and CD8 markers, and Th1-type cytokines, suggesting active WHV-specific T lymphocytes. Immunosuppression for 12 weeks using cyclosporine A in such woodchucks resulted in transient reactivation of WHV replication. Serum of 1 woodchuck that became positive for WHV DNA during immunosuppression was inoculated into WHV-susceptible woodchucks, and a productive infection was demonstrated. The results indicate that after infection durable cellular immunity to WHV is essential for the long-term control of viral replication and is probably maintained by continuous priming from residual virus.


CONCLUSIONS
These experimental observations demonstrate the potential of immunosuppression to reactivate HBV after resolution of infection.
Menne
Stephan
S
Gastrointestinal Unit, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. sm119@cornell.edu
Cote
Paul J
PJ
Butler
Scott D
SD
Toshkov
Ilia A
IA
Gerin
John L
JL
Tennant
Bud C
BC
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D004279:DNA, Viral / Q000097:blood; D006509:Hepatitis B / Q000276:immunology / Q000662:veterinary*; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008392:Marmota / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology / Q000502:physiology*
D000956:Antigens, Viral; D004279:DNA, Viral; D007166:Immunosuppressive Agents; D016572:Cyclosporine