The Molecular Mechanisms of Autophagy-Virus Interactions: From Antiviral Defense to Viral Counterstrategies

Abstract

Autophagy is a highly conserved cellular degradative pathway in eukaryotes that exerts a dual regulatory role in the host antiviral defense. On the one hand, as an essential component of the host antiviral defense network, autophagy participates in the direct degradation of viral components, synergistically modulates innate immune signaling pathways including TLRs, RLRs, and cGAS-STING, and regulates adaptive immune responses such as MHC class I/II-mediated antigen presentation. On the other hand, diverse viruses have evolved sophisticated immune evasion mechanisms during long-term coevolution with the host. These viruses target key steps of autophagy, including initiation, membrane nucleation, elongation, maturation, and lysosomal fusion, to hijack or suppress the autophagic pathway and facilitate their replication. The regulation of autophagy by different viruses exhibits remarkable molecular specificity. In-depth dissection of these molecular mechanisms underlying autophagy-virus interactions will provide novel insights into the pathogenesis of viral diseases. This review systematically summarizes the core process of autophagy and its multiple regulatory mechanisms in antiviral immunity. We further highlight how viruses employ specific molecular strategies to target distinct stages of autophagy during infection, thereby hijacking the autophagic pathway to complete their replication cycles and pathogenic progression.