Viral suppression of the interferon system

This review comprehensively examined the diverse strategies employed by viruses to evade and suppress the host type I interferon (IFN) system, a central component of innate antiviral immunity. The authors synthesized mechanistic evidence across a broad range of RNA and DNA viruses to illustrate how viral proteins interfere with interferon induction, signaling, and downstream antiviral effector functions at multiple levels of the host defense cascade. They described how viruses such as influenza virus, paramyxoviruses, hepatitis C virus, rabies virus, hantaviruses, and herpesviruses specifically target key innate immune sensors and signaling intermediates, including RIG-I, MDA5, IPS-1/MAVS, TBK1, IRF3, and NF-κB, thereby preventing IFN production. The review further highlighted viral antagonism of interferon-activated JAK–STAT signaling through degradation, sequestration, or inactivation of STAT proteins, as exemplified by the V and C proteins of paramyxoviruses, rabies virus phosphoprotein P, and Ebola virus VP24. In addition, the authors discussed how many viruses directly inhibit interferon-stimulated antiviral effectors such as PKR, RNase L, and the 2′–5′ oligoadenylate synthetase pathway through dsRNA sequestration, pseudosubstrate mimicry, translational shutoff, or manipulation of host regulatory factors. Importantly, the review emphasized that viruses have evolved both highly specialized interferon antagonists and multifunctional structural or replication-associated proteins with secondary immune evasion roles, reflecting strong evolutionary pressure to overcome host innate defenses. Overall, the article provides a broad conceptual framework for understanding viral interferon escape mechanisms and highlights how this knowledge can be leveraged for the development of attenuated vaccines and interferon-sensitive oncolytic virotherapies.
(TMR)