Interferons: Success in anti-viral immunotherapy

Abstract

The interferons (IFNs) are glycoproteins with strong antiviral activities that represent one of the first lines of host defense against invading pathogens. These proteins are classified into three groups, Type I, II and III IFNs, based on the structure of their receptors on the cell surface. Due to their ability to modulate immune responses, they have become attractive therapeutic options to control chronic virus infections. In combination with other drugs, Type I IFNs are considered a “standard of care” in suppressing Hepatitis C (HCV) and Hepatitis B (HBV) infections, while Type III IFN has generated encouraging results as a treatment for HCV infection in phase III clinical trials. However, though effective, using IFNs as a treatment is not without the need for caution. IFNs are such powerful cytokines that affect a wide array of cell types; as a result, patients usually experience unpleasant symptoms, with a percentage of patients suffering system wide effects. Thus, constant monitoring is required for patients treated with IFN in order to reach the treatment goals of suppressing virus infection and maintaining quality of life.

Type I Interferons: Distinct Biological Activities and Current Applications for Viral Infection

“…Activation gives rise to the activation of ISGs via recognition of upstream sequence elements in promoters and formation of antiviral proteins such as OAS, PKR, ISG and Mx, which exert distinct biological activities (Fig. 1) [2, 12-14]. The differences among type I IFN classes is prominent compared to these common points.…”

“…Interferons (IFN) were initially described in 1957 as soluble glycoproteins with strong antiviral effects [1, 2]. Three types of IFNs, types I, II and III, have been classified based on of their genetic, structural, and functional characteristics and their cell-surface receptors [3].…”

“…IFN biological activities include antiviral, antiproliferative and immunomodulatory effects in the host response to viral or bacterial infection. As a result, IFN induction is a powerful tool in the host response to cancer or viral infection [2]. Type I IFNs, specifically IFN-α and IFN-β, are part of the standard treatment for chronic hepatitis B and C virus infections.…”

Understanding Interferon Subtype Therapy for Viral Infections: Harnessing the Power of the Innate Immune System.

“…As shown in Fig. 1, there are three major IFN types (Type I, II and III) with multiple proteins that bind their receptors in an autocrine and paracrine manner, leading to expression of thousands of genes, having various biological properties in antimicrobial defense [7]. IFNs are highly conserved across species (e.g.…”

“…Such treatments with these limited subtypes overlook the possible therapeutic potential of the other natural IFN subtypes with divergent biological functions. Furthermore, although most IFNs are biologically active in the picomolar range, conventional IFN treatment uses systemic administration of extraordinary high doses, often associated with severe side effects including neurological toxicity limiting treatment efficacy [7,33,34]. Alternative treatment regimes using low dose IFN application, directed to the mucosal immune system, have shown improved clinical efficacy against virus infection in an experimental setting [34][35][36][37].…”