Direct Antiviral Mechanisms of Interferon-Gamma

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.