The mode of action of interferons in viral infections and their possible role in the control of hepatitis B

Abstract

Interferons can alter the course of virus infections by inhibiting virus replication at the intracellular level and by modifying the aspecific and specific immune response to viral antigens in body fluids and on cellular surfaces. Treatment of isolated cells with interferon renders them resistant to infections by viruses belonging to virtually any family. Knowledge of the mechanism of this effect is derived from studies employing both DNA (especially vaccinia virus and SV40) and RNA-viruses (especially picorna-, toga-, rhabdo-, reo- and retroviruses). Interferon induces multiple alterations in the level and state of intracellular regulatory molecules, leading to inhibition of virus replication at several possible steps. In the case of certain DNA viruses, transcription of viral DNA seems to be inhibited. In the case of RNA viruses the target for interferon action is mainly translation. The retroviridae constitute a special case and, in view of their analogy with the hepadnaviridae, are of particular relevance to the possible effects of interferon on the replication of HBV. Interferon inhibits one or more initial stages of primary infection of cells by transforming or nontransforming retroviruses, thereby preventing or delaying the synthesis and/or integration of viral DNA. In cells that already contain an integrated and fully expressed retrovirus genome, interferon treatment results in a reduced release of viral particles as well as a downward shift of the ratios between the numbers of infectious vs noninfectious particles. Immuno-modulatory properties of interferon which might alter the course of HBV-infection include: potentiation of cytotoxic activity of lymphocytes and macrophages; direct anti-inflammatory effects; enhancement or depression in antibody formation. How important the individual and global contribution of these effects are in determining the outcome of a primary or chronic HBV infection has so far not been established. The main reason for this is the lack of suitable animal model systems for HBV-infection. Interferons-α and -β, being induced by viral replicative events in cells of any kind, are likely to be relatively important at early phases of an infection. Interferon-γ, being formed as a result of the establishment of antigen-sensitized T cells is likely to exert its effect during later stages or during chronic infection. © 1986 Elsevier Science Publishers, Amsterdam All rights reserved.