Hijacking and subversion of macrophage antiviral functions by viruses

Macrophages are frontline effectors of innate immunity, acting as essential elements for clearing pathogens. However, viruses have continuously evolved sophisticated mechanisms to subvert these critical defenses. This review comprehensively decodes how viral pathogens systematically dismantle macrophage microbicidal capacities. It delineates the evasion of pattern recognition receptor surveillance, the hijacking of endocytic trafficking, and the active arrest of phagolysosomal maturation to secure intracellular replication niches. Furthermore, the review explores the paradoxical viral manipulation of the host oxidative burst, where pathogens weaponize reactive oxygen species or exploit antioxidant machineries, driving severe redox dysregulation. Profound metabolic reprogramming, including shifts toward aerobic glycolysis and the skewing of inflammatory polarization alongside cell death pathways, is also examined. Ultimately, these evasion strategies inflict functional paralysis on macrophages, heavily predisposing hosts to severe secondary bacterial coinfections. Mapping this virus-host crosstalk highlights critical vulnerabilities, providing a foundation for novel host-directed antiviral immunotherapies.