The HN protein of Newcastle disease virus induces cell apoptosis through the induction of lysosomal membrane permeabilization.

Lysosomes are acidic organelles that mediate the degradation and recycling of cellular waste materials. Damage to lysosomes can cause lysosomal membrane permeabilization (LMP) and trigger different types of cell death, including apoptosis. Newcastle disease virus (NDV) can naturally infect most birds. Additionally, it serves as a promising oncolytic virus known for its effective infection of tumor cells and induction of intensive apoptotic responses. However, the involvement of lysosomes in NDV-induced apoptosis remains poorly understood. Here, we demonstrate that NDV infection profoundly triggers LMP, leading to the translocation of cathepsin B and D and subsequent mitochondria-dependent apoptosis in various tumor and avian cells. Notably, the released cathepsin B and D exacerbate NDV-induced LMP by inducing the generation of reactive oxygen species. Additionally, we uncover that the viral Hemagglutinin neuraminidase (HN) protein induces the deglycosylation and degradation of lysosome-associated membrane protein 1 (LAMP1) and LAMP2 dependent on its sialidase activity, which finally contributes to NDV-induced LMP and cellular apoptosis. Overall, our findings elucidate the role of LMP in NDV-induced cell apoptosis and provide novel insights into the function of HN during NDV-induced LMP, which provide innovative approaches for the development of NDV-based oncolytic agents. Author summary: Our study investigates the role of lysosomes in Newcastle disease virus (NDV)-induced cell apoptosis. We found that NDV infection leads to lysosomal membrane permeabilization (LMP) and the release of cathepsin B and D enzymes. This triggers mitochondria-dependent apoptosis in various tumor and avian cells. The released cathepsin B and D exacerbate LMP by generating reactive oxygen species. Additionally, the viral Hemagglutinin neuraminidase protein degrades lysosome-associated membrane proteins (LAMP1 and LAMP2), contributing to LMP and apoptosis. These findings provide insights into NDV-induced cell apoptosis and highlight the potential of targeting lysosomes for the development of NDV-based oncolytic therapies. [ABSTRACT FROM AUTHOR]

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