Feedback circuits in hepatitis B virus infection.
A simplified model using kinetic logic is proposed to approach the problem after Hepatitis B viral (HBV) infection. It accounts for several stable regimes or attractors corresponding to the essential dynamic behaviour of the replication of the Hepatitis B virus. Infection with the virus can result in viral clearance, fulminant hepatic failure and death, or chronic transmissible infection, that is multistationarity corresponding to the existence of the positive feedback circuit in our modelling. Another implication of this model is the existence of oscillations or homeostatic mechanisms, sometimes observed in the viral cycle, consistent with the existence of the negative feedback circuit. Thus, this report shows how a simple model of kinetic logic may be used to account for the variety of manifestations of HBV infection. This model implies the presence of the Hepatitis B e antigen, whose conservation suggests that it plays an important role in the life cycle of hepadnaviruses. Its function in the viral cycle is still unknown, but our model suggests that this antigen could explain the passage from one state of the viral infection (acute or latent) to another, as well as the oscillatory behavior which may account for the intermittent symptoms of hepatitis observed in some patients. Furthermore, this model shows a virgin state. This state is also reached after recovery. The model proposed demonstrates that starting from a viral acute infection, the host's immune response, depending on the immunological status of the patient, can lead to viral clearance, or to periodic spontaneous reactivation.
Martinet-Edelist
Claire
C
Virologie moléculaire et structurale, CNRS, 91198 Gif/Yvette, France. edelist@gv.cnrs-gif.fr
D000208:Acute Disease; D018450:Disease Progression; D005246:Feedback / Q000502:physiology*; D006509:Hepatitis B / Q000276:immunology / Q000821:virology*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000821:virology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007700:Kinetics; D016015:Logistic Models; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014775:Virus Activation / Q000502:physiology; D014779:Virus Replication / Q000502:physiology*
D006513:Hepatitis B e Antigens