Development of an apoptotic lentogenic Newcastle disease virus strain by incorporating the p30 protein of African swine fever virus

Abstract

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.