Abstract
Chronic hepatitis B virus (HBV) infection imposes a severe burden on global public health. Currently, there are no curative therapies for millions of chronic HBV-infected patients (Lok et al., 2017). Interferon (IFN; including pegylated IFN) is an approved anti-HBV drug that not only exerts direct antiviral activity, but also augments immunity against HBV infection. Through a systematic review of the literature, here we summarize and present recent progress in research regarding the interactions between IFN and HBV as well as dissect the antiviral mechanisms of IFN. We focus on inhibition of HBV replication by IFN-stimulated genes (ISGs) as well as inhibition of IFN signaling by HBV and viral proteins. Finally, we briefly discuss current IFN-based HBV treatment strategies. This review may help to better understand the mechanisms involved in the therapeutic action of IFN as well as the crosstalk between IFN and HBV, and facilitate the development of both direct-acting and immunology-based new HBV drugs.
Highlights
More than 50 years have passed since the identification of human hepatitis B virions, initially named “Dane particles,” in the late 1960s; and hepatitis B virus (HBV) infection remains a serious global health problem (Hirschman et al, 1969; Cossart and Field, 1970; Dane et al, 1970; ZanenLim, 1976; Glebe, 2007)
This review consists of three sections: (1) the HBV life cycle and the classical IFN induction pathway in response to viral infection; (2) a systematic discussion of the crosstalk between IFN and HBV, with a focus on two-way inhibition: the inhibition of HBV infection and replication by IFN-stimulated genes (ISGs) as well as the inhibition of IFN signaling by HBV and HBV proteins; and (3) a brief discussion of the current IFN-based HBV treatment strategies
DNA is sensed by DEAD-box protein (DDX) 41, cyclic GMP-AMP synthase, and γ-IFNinducible protein 16 (IFI16) (Unterholzner et al, 2010; Zhang et al, 2011; Sun et al, 2013; Bhat and Fitzgerald, 2014), all of which lead to the activation of stimulator of IFN genes (STING)
Summary
Specialty section: This article was submitted to Infectious Diseases, a section of the journal Frontiers in Microbiology. Chronic hepatitis B virus (HBV) infection imposes a severe burden on global public health. There are no curative therapies for millions of chronic HBV-infected patients (Lok et al, 2017). Interferon (IFN; including pegylated IFN) is an approved antiHBV drug that exerts direct antiviral activity, and augments immunity against HBV infection. Through a systematic review of the literature, here we summarize and present recent progress in research regarding the interactions between IFN and HBV as well as dissect the antiviral mechanisms of IFN. We briefly discuss current IFN-based HBV treatment strategies. This review may help to better understand the mechanisms involved in the therapeutic action of IFN as well as the crosstalk between IFN and HBV, and facilitate the development of both direct-acting and immunology-based new HBV drugs
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