Bora Nilave Ranjan, Kumar Rakesh, Kumar Sachin
Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India.
Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, 781039, India.
Virology. 2025 May;606:110477. doi: 10.1016/j.virol.2025.110477. Epub 2025 Mar 1.
Virotherapy is one of the emerging approaches for cancer treatment. Newcastle disease virus (NDV) is a well-studied avian paramyxovirus commonly isolated from birds. Typically, the virulent strains of NDV are acknowledged for their oncolytic properties. The anti-tumor effects of NDV rely on its capacity to trigger apoptosis in cancer cells and elicit inflammatory immune responses against the tumor. However, the virulent strains pose significant challenges for clinical application. This study investigated the development of an apoptotic lentogenic strain of NDV by incorporating the p30 protein gene of the African swine fever virus (ASFV). Previous studies have indicated that the p30 protein interacts with various cellular proteins, including PARP9 and DAB2, which suggests its potential for direct or indirect influence on apoptotic pathways. Our initial data confirmed the upregulation of caspase 3/9, PARP, and cytochrome c, suggesting the pro-apoptotic nature of the p30 protein. Further, a recombinant NDV (rNDV) expressing p30 protein (rNDV-p30) was developed, and its effects were evaluated on human breast cancer (MCF-7) cells. While rNDV alone can't show apoptosis, its variant, rNDV-p30 showed promising apoptotic features in MCF-7 cells. Overall, the results demonstrated the development of rNDV-p30 as an apoptotic virus that offered a novel virotherapy strategy for cancer treatment. Additional research is needed to investigate the underlying mechanisms, safety, and efficacy of the apoptotic activity of the rNDV-p30 and to evaluate the effectiveness of this approach in animal models.
病毒疗法是癌症治疗的新兴方法之一。新城疫病毒（NDV）是一种经过充分研究的禽副粘病毒，通常从鸟类中分离出来。典型地，NDV的强毒株因其溶瘤特性而受到认可。NDV的抗肿瘤作用依赖于其触发癌细胞凋亡并引发针对肿瘤的炎性免疫反应的能力。然而，强毒株在临床应用中带来了重大挑战。本研究通过整合非洲猪瘟病毒（ASFV）的p30蛋白基因，研究了一种凋亡性弱毒株NDV的开发。先前的研究表明，p30蛋白与多种细胞蛋白相互作用，包括PARP9和DAB2，这表明其对凋亡途径具有直接或间接影响的潜力。我们的初步数据证实了caspase 3/9、PARP和细胞色素c的上调，表明p30蛋白具有促凋亡性质。此外，开发了一种表达p30蛋白的重组NDV（rNDV-p30），并评估了其对人乳腺癌（MCF-7）细胞的影响。虽然单独的rNDV不会显示凋亡，但它的变体rNDV-p30在MCF-7细胞中显示出有前景的凋亡特征。总体而言，结果证明了rNDV-p30作为一种凋亡病毒的开发，为癌症治疗提供了一种新的病毒疗法策略。需要进一步的研究来调查rNDV-p30凋亡活性的潜在机制、安全性和有效性，并评估这种方法在动物模型中的有效性。
