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Antiviral interferons induced by Newcastle disease virus (NDV) drive a tumor-selective apoptosis.

ABSTRACT: Newcastle disease virus (NDV) strongly induces both type I and III antiviral interferons (IFNs-?/-? and IFN-?, respectively) in tumor cells while it induces mainly type III IFN in normal cells. Impairment of antiviral type I IFN signaling in tumor cells is thought to be the reason for effective oncolysis. However, there is lack of clarity why lentogenic strain NDV can also induce oncolysis. NDV infection caused apoptosis in normal and tumor cells as demonstrated with the caspase-3 enzyme activation and annexin-V detection. The apoptosis response was inhibited by B18R protein (a type I IFN inhibitor) in tumor cells i.e. A549 and U87MG, and not in normal cells i.e. NB1RGB and HEK293. Similarly, UV-inactivated medium from NDV infection was shown to induce apoptosis in corresponding cells and the response was inhibited in A549 and U87MG cells with the addition of B18R protein. Treatment with combination of IFNs-?/-?/-? or IFNs-?/-? or IFN-? in NB1RGB, HEK293, A549 and U87MG showed that caspase activity in IFNs-?/-?/-? group was the highest, followed with IFN-?/-? group and IFN-? group. This suggests that tumor-selectivity of NDV is mainly because of the cumulative effect of type I and III in tumor cells that lead to higher apoptotic effect.

SUBMITTER: Ginting TE

PROVIDER: S-EPMC6806003 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Antiviral interferons induced by Newcastle disease virus (NDV) drive a tumor-selective apoptosis.

Ginting Teridah Ernala TE Christian Salomo S Larasati Young Othiwi YO Suryatenggara Jeremiah J Suriapranata Ivet Marita IM Mathew George G

Scientific reports 20191022 1

Newcastle disease virus (NDV) strongly induces both type I and III antiviral interferons (IFNs-α/-β and IFN-λ, respectively) in tumor cells while it induces mainly type III IFN in normal cells. Impairment of antiviral type I IFN signaling in tumor cells is thought to be the reason for effective oncolysis. However, there is lack of clarity why lentogenic strain NDV can also induce oncolysis. NDV infection caused apoptosis in normal and tumor cells as demonstrated with the caspase-3 enzyme activat ...[more]

PMID: 31641164

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Project description:Newcastle disease (ND) and infectious bronchitis (IB) are two highly contagious diseases that severely threaten the poultry industry. The goal of this study is to prevent these two diseases and reduce the vaccine costs during storage and transportation. In this study, we design a thermostable recombinant Newcastle disease virus (NDV) candidate live vaccine strain designated as rLS-T-HN-T/B, which expresses the multiple epitope cassette of the identified infectious bronchitis virus (IBV) (S-T/B). The rLS-T-HN-T/B strain was found to possess similar growth kinetics, passage stability, morphological characteristics, and virulence to the parental LaSota strain. After incubation at 56 °C at the indicated time points, the rLS-T-HN-T/B strain was determined by the hemagglutination (HA), and 50% embryo infectious dose (EID50) assays demonstrated that it accords with the criteria for thermostability. The thermostable rLS-T-HN-T/B and parental LaSota vaccines were stored at 25 °C for 16 days prior to immunizing the one-day-old specific pathogen-free (SPF) chicks. Three weeks postimmunization, the virus challenge results suggested that the chicks vaccinated with the rLS-T-HN-T/B vaccine were protected by 100% and 90% against a lethal dose of NDV and IBV, respectively. Furthermore, the trachea ciliary activity assay indicated that the mean ciliostasis score of the chicks vaccinated with thermostable rLS-T-HN-T/B vaccine was significantly superior to that of the LaSota and PBS groups (p < 0.05). The rLS-T-HN-T/B vaccine stored at 25 °C for 16 days remained capable of eliciting the immune responses and protecting against IBV and NDV challenges. However, the same storage conditions had a great impact on the parental LaSota strain vaccinated chicks, and the NDV challenge protection ratio was only 20%. We conclude that the thermostable rLS-T-HN-T/B strain is a hopeful bivalent candidate vaccine to control both IB and ND and provides an alternative strategy for the development of cost-effective vaccines for village chickens, especially in the rural areas of developing countries.

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Antiviral interferons induced by Newcastle disease virus (NDV) drive a tumor-selective apoptosis.

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Antiviral interferons induced by Newcastle disease virus (NDV) drive a tumor-selective apoptosis.

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