Lumpy skin disease virus strategically modulates autophagy to facilitate viral replication in MDBK cells.

Lumpy Skin Disease Virus (LSDV), a Capripoxvirus of significant veterinary and economic importance, has been reported to manipulate host cellular processes, including autophagy, to enhance its replication and persistence. However, the precise mechanisms by which LSDV interacts with autophagy remain unclear. This study investigates the effect of LSDV infection on host autophagic pathways in MDBK cells, focusing on autophagic flux modulation and its implications for viral replication. Western blot and immunofluorescence analyses demonstrated that LSDV does not robustly induce autophagy but interferes with autophagic flux by suppressing lysosomal degradation, as indicated by reduced LAMP2 expression at later stages of infection. Pharmacological modulation of autophagy using activators (Rapamycin, Torin 2) and inhibitors (Bafilomycin A1, MRT68921) revealed that increased autophagy enhanced LSDV replication, whereas inhibition of autophagy significantly impaired viral propagation, underscoring the virus's reliance on autophagic processes for efficient replication. Notably, cells infected with BEI-inactivated LSDV exhibited significantly higher LC3B II accumulation than those infected with live LSDV, suggesting that active viral replication is required for autophagy modulation. Additionally, dose-dependent analysis revealed that LSDV-mediated suppression of LC3B II was most prominent at higher viral titers, further confirming the virus's capacity to regulate host autophagic responses. These findings suggest that LSDV strategically modulates autophagy by maintaining basal autophagic levels while suppressing lysosomal degradation, allowing for optimal viral replication. Understanding the interplay between LSDV and autophagy provides novel insights into its pathogenesis and identifies potential antiviral targets to mitigate LSDV infections in cattle.