Direct Antiviral Mechanisms of Interferon-Gamma

Abstract

Interferon-gamma (IFNG) is a pleiotropic cytokine that modulates both innate and adaptive immune networks; it is the most potent activator of macrophages and a signature cytokine of activated T lymphocytes. Though IFNG is now appreciated to have a multitude of roles in immune modulation and broad-spectrum pathogen defense, it was originally discovered, and named, as a secretory factor that interferes with viral replication. In contrast to the prototypical type I interferons produced by any cells upon viral infection, only specific subsets of immune cells can produce IFNG upon infection or stimulation with antigen or mitogen. Still, virtually all cells can respond to both types of interferons. This makes IFNG a versatile anti-microbial cytokine and also gives it a unique position in the antiviral defense system. The goal of this review is to highlight the direct antiviral mechanisms of IFNG, thereby clarifying its antiviral function in the effective control of viral infections.

Pathogenic Th1 responses in CHIKV‐induced inflammation and their modulation upon Plasmodium parasites co‐infection

“…In the context of sequential Plasmodium‐ CHIKV co‐infection, the abrogation of viremia was reverted in mice lacking IFNγ and in wildtype mice treated with IFNγ neutralizing antibodies . The induced IFNγ by pre‐existing Plasmodium infection could exert an antiviral activity through the priming of primary CHIKV targets such as fibroblasts, myocytes, endothelial cells, and macrophages during the early stages of infection (Figure ). Particularly, endothelial cells and fibroblasts have been shown to display antiviral ability upon IFNγ stimulation by interfering with virus gene transcription and by increasing their responsiveness to viral nucleic acids .…”

“…51,63 In the context of sequential Plasmodium-CHIKV co-infection, the abrogation of viremia was reverted in mice lacking IFNγ and in wildtype mice treated with IFNγ neutralizing antibodies. 119 The induced IFNγ by pre-existing Plasmodium infection could exert an antiviral activity through the priming of primary CHIKV targets such as fibroblasts, myocytes, endothelial cells, and macrophages during the early stages of infection 13,127,128 (Figure 2).…”

MERS-CoV Spike Protein Vaccine and Inactivated Influenza Vaccine Formulated with Single Strand RNA Adjuvant Induce T-Cell Activation through Intranasal Immunization in Mice

“…According to Figure 6, IFN-γ-producing T-cells, which may play a role in protecting against virus infection [41], were increased in the RNA adjuvant formulated influenza vaccine. Thus, the RNA adjuvant increases IFN-γ-producing T-cells, contributing to the antiviral effect.…”

Significance of RANTES‐CCR5 axis and linked downstream immunomodulation in Dengue pathogenesis: A study from Guwahati, India

“…IFN-γ plays antiviral function to protect against viral infection. 44,45 The serum IFN-γ level was found to be increased only in the mild Dengue cases compared to controls, but not in severe Dengue cases. The differential modulation of IL-12 may be an influencing factor as IL-12 is known to induce IFN-γ expression.…”