Syncytia generated by hemagglutinin-neuraminidase and fusion proteins of virulent Newcastle disease virus induce complete autophagy by activating AMPK-mTORC1-ULK1 signaling>

Hemagglutinin-neuraminidase and fusion proteins of virulent Newcastle disease virus cooperatively disturb fusion–fission homeostasis to enhance mitochondrial function by activating the unfolded protein response of endoplasmic reticulum and mitochondrial stress

“…However, the roles of the fusion (F) and hemagglutinin-neuraminidase (HN) glycoproteins of Newcastle disease virus (NDV) in mitochondrial have yet to be studied. Our previous study suggested that the F and HN of virulent NDV synergistically induced significant syncytium formation accompanied with complete autophagic flux in DF-1 and A549 cells [4]. As describe in our previous data [4], A549 cell line can be used as a cell model to study the function of both NDV glycoproteins (Flag-F and HA-HN) of NDV, which are constructed on the basis of the sequence of an F48E9 strain (Genbank Accession Number: MG456905), a standard velogenic strain.…”

ATM-mediated DNA double-strand break response facilitated oncolytic Newcastle disease virus replication and promoted syncytium formation in tumor cells

“…The typical lesion of virulent NDV infection is syncytium formation and membrane fusion in chicken embryo fibroblast (DF-1) and adenocarcinomic human alveolar basal epithelial (A549) cells [31], indicating that both cell lines can be cell models for further research. To observe the effect of syncytium formation on subcellular structures, we used phalloidin fluorescent conjugates to label endogenous F-actin filaments in A549 cells, which bind only to the polymeric and oligomeric forms of F-actin.…”

“…https://doi.org/10.1371/journal.ppat.1008514.g007 It then triggers F protein conformational changes and releases fusion peptides to fuse the viral and cellular membranes [29,30]. Meanwhile, after transfection, the inactive precursor of F protein (F 0 ) is proteolytically cleaved by the host-cell protease at the cleavage site and forms a biologically active protein comprising the disulfide-linked F 1 +F 2 heterodimer [29][30][31]. After a series of proteolytic processing and conformational changes, the fusogenically active F 1 protein and HN form an F+HN complex via the interaction between a stalk and an HRB domain [29,30].…”

“…Both viral protein plasmids were constructed based on the F48E9 strain sequence (GenBank accession number MG456905), a standard velogenic strain. Seven F protein mutation plasmids were successfully constructed following the manufacturer's instruction for the Mut Express Multis Fast Mutagenesis Kit V2 (Vazyme, Nanjing, China) [31]. The pCAGGS-F49E9-N-myc-L (abbreviated as "pCAGGS-myc-L") plasmid was also constructed based on the sequence of F48E9 strain with the following primers:…”

“…NDV infects target tumor cells through HN-mediated attachment and then triggers F protein conformational change. Finally, it releases fusion peptide to fuse the viral and cellular membrane [29,30], which generates typical syncytium lesions [31]. Considering the possible link between syncytium lesions and DNA damage, we aimed to elucidate the connections among membrane fusion, oncolytic NDV replication, and DDR in the present study.…”