Effects of Interferon-α/β on HBV Replication Determined by Viral Load

PLoS Pathogens

Jing-hsiung James Ou¹  Wen-ling Chen¹  Yongjun Tian¹ 

[1] Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America

关键词: Viral replication;    Mouse models;    DNA replication;    Hepatitis B virus;    Mammalian genomics;    Interferons;    Viral load;    Genetic interference;   

DOI  :  10.1371/journal.ppat.1002159

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Interferons α and β (IFN-α/β) are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV) patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low.

【 授权许可】

CC BY