Autophagy in VZV infection: To degrade, or to deliver?

Varicella-zoster virus (VZV) interacts with autophagy in a manner distinct from that of many other herpesviruses. Rather than broadly blocking autophagic flux, VZV generally induces a functional autophagic response and appears to use this pathway to support productive infection. Available data suggest that autophagy mainly plays a pro-viral role during the VZV lytic cycle in epithelial cells and fibroblasts by promoting viral glycoprotein maturation, secondary envelopment, intracellular trafficking, and egress. However, emerging evidence indicates that autophagy can exert antiviral and protective effects in neuronal cells and hematopoietic cells, highlighting the cell-type-dependent duality of autophagy in VZV infection. A notable feature of this process is the convergence of autophagic and endosomal pathways, through which VZV redirects autophagy-related vesicle trafficking away from lysosomal degradation and toward transport and exocytosis. Mechanistically, ER stress-UPR signaling acts as a major upstream regulator of VZV-induced autophagy, while the contributions of mTOR, ESCRT, and TLR-related pathways remain to be fully elucidated. This review summarizes recent advances in the mechanisms, functions, and cell-context dependence of VZV-autophagy interactions and highlights key unresolved questions relevant to viral pathogenesis and host-directed antiviral strategies.