Document Type : Original Article
Author
Department of Agricultural Biotechnology, College of Biotechnology, University of Al-Qadisiyah, Al-Diwaniyah, Iraq
Abstract
Introduction: Newcastle disease virus (NDV) is a candidate oncolytic virus. This study assessed the preferential in vitro effects of the attenuated LaSota NDV strain in p53-deficient H1299 non-small cell lung cancer (NSCLC) cells compared with BEAS-2B bronchial epithelial cells.
Materials and Methods: H1299 and BEAS-2B cells were infected with NDV LaSota at multiplicities of infection (MOIs) of 1, 5, and 10 and evaluated at 24, 48, and 72 h post-infection. MTT reduction, cytopathic effect (CPE) microscopy, Annexin V-FITC/PI flow cytometry, glucose and lactate measurements, intracellular ATP assays, and hemagglutination (HA) assays were performed. Each condition was assessed in three independent experiments. Publicly available LaSota-NDV RNA-seq data from KKU-055 and KKU-100 cells (NCBI BioProject PRJNA1114906) were used for cross-cancer molecular validation.
Results: NDV induced a time- and MOI-dependent reduction in MTT-based metabolic activity that was more pronounced in H1299 than in BEAS-2B cells. H1299 cells also exhibited greater CPE severity, higher Annexin V-positive fractions, and more pronounced reductions in glucose consumption, lactate production, and intracellular ATP. At 48 h post-infection, HA titers increased with MOI, reflecting hemagglutinating activity; however, HA titers are not equivalent to infectious virus titers. In the external dataset, LaSota NDV was associated with 368 differentially expressed genes (DEGs) in KKU-055 cells (321 upregulated and 47 downregulated) and 1,807 DEGs in KKU-100 cells (892 upregulated and 915 downregulated). In total, 131 genes were commonly altered, including six shared hub genes (DDX58, IFIH1, IRF7, ISG15, GBP1, and DHX58), consistent with involvement of apoptosis, interferon, TNF-α/NF-κB, and IL-6/JAK/STAT3 pathways.
Conclusions: H1299 cells exhibited a preferential in vitro response to LaSota NDV across multiple cellular and metabolic parameters. However, direct evidence of infectious viral replication and its relationship to cytotoxicity remains to be established. Transcriptomic data support a distinction between cell-killing programs in H1299 cells and the comparatively preserved responses in BEAS-2B cells. Further studies are required to confirm infectious virus production and in vivo relevance.
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