Recombinant Newcastle disease virus harboring PTEN suppresses pancreatic ductal adenocarcinoma growth by inhibiting PI3K/AKT/mTOR signaling and promoting apoptosis

Deleted Journal, Journal Year: 2024, Volume and Issue: 32(4), P. 200898 - 200898

Published: Oct. 30, 2024

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and intractable cancer that requires more effective therapies can improve early detection, enhance treatment efficacy, provide better patient outcomes. Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations reduced phosphatase tensin (PTEN) protein expression are key factors driving the proliferation severity of PDAC. To address this, recombinant Newcastle disease virus (rNDV) containing PTEN gene (rNDV-PTEN) was created to investigate its PDAC cell-killing tumor-suppression effects in cells transplanted into mice. induced by rNDV-PTEN infection KRAS-mutated lowered phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT)/mammalian target rapamycin (mTOR) signaling, promoted cell death, suppressed tumor growth. overexpression promotes apoptotic signaling pathways both PANC-1 orthotopic xenograft Additionally, during virotherapy, rNDV-PTEN-injected mice exhibited mild immune response no abnormal responses blood parameters such as glucose, triglyceride, total cholesterol levels. These findings support potential safe therapy for with activated PI3K/AKT/mTOR caused KRAS mutations. Thus, gene-containing rNDV may be promising candidate pancreatic treatment.

Language: Английский

The Role of Dual Mutations G347E and E349D of the Pigeon Paramyxovirus Type 1 Hemagglutinin–Neuraminidase Protein In Vitro and In Vivo

Veterinary Sciences, Journal Year: 2024, Volume and Issue: 11(12), P. 592 - 592

Published: Nov. 25, 2024

Pigeon Newcastle disease (ND) is the most common viral infectious in pigeon industry, caused by paramyxovirus type 1 (PPMV-1), a variant of chicken-origin virus (NDV). Previous studies have identified significant amino acid differences between PPMV-1 and NDV at positions 347 349 hemagglutinin-neuraminidase (HN) protein, with predominantly exhibiting glycine (G) position glutamic (E) 349, while NDVs show E aspartic (D) 349. However, impact these substitutions remains unclear. In this study, we generated recombinant virus, NT-10-G347E/E349D, introducing G347E E349D dual mutations into strain NT-10 using reverse genetics. The biological characteristics NT-10-G347E/E349D were compared both vitro vivo. vitro, reduce NT-10's replication neuraminidase activity embryo fibroblast (PEF) cells enhancing chicken (CEF) cells. Additionally, decrease binding affinity to α-2,6 sialic receptor significantly increasing its for α-2,3 receptor. vivo, exhibited reduced pathogenicity pigeons but increased chickens parental strain. also pigeon-to-pigeon transmission enhanced from chickens. Notably, antigenic observed as an inactivated vaccine based on provided full protection against challenge immunized only 67% mortality NT-10-G347E/E349D. Overall, findings underscore critical role acids infection, pathogenicity, transmission, providing theoretical foundation scientific prevention control PPMV-1.

Language: Английский