Newcastle disease vaccines-A solved problem or a continuous challenge?

Newcastle disease virus (NDV) causes severe infectious disease in poultry and selectively kills tumor cells, by inducing apoptosis and cytokines secretion. In this report, we study the mechanisms underlying NDV-induced apoptosis by investigating the unfolded protein response (UPR). We found that NDV infection activated all three branches of the UPR signaling (PERK-eIF2α, ATF6, and IRE1α) and triggered apoptosis, in avian cells (DF-1 and CEF) and in various human cancer cell types (HeLa, Cal27, HN13, A549, H1299, Huh7, and HepG2). Interestingly, the suppression of either apoptosis or UPR led to impaired NDV proliferation. Meanwhile, the inhibition of UPR by 4-PBA protected cells from NDV-induced apoptosis. Further study revealed that activation of PERK-eIF2α induced the expression of transcription factor CHOP, which subsequently promoted apoptosis by downregulating BCL-2/MCL-1, promoting JNK signaling and suppressing AKT signaling. In parallel, IRE1α mediated the splicing of XBP1 mRNA and resulted in the translation and nuclear translocation of XBP1s, thereby promoting the transcription of ER chaperones and components of ER-associated degradation (ERAD). Furthermore, IRE1α promoted apoptosis and cytokines secretion via the activation of JNK signaling. Knock down and overexpression studies showed that CHOP, IRE1α, XBP1, and JNK supported efficient virus proliferation. Our study demonstrates that the induction of eIF2α-CHOP-BCL-2/JNK and IRE1α-XBP1/JNK signaling cascades promote apoptosis and cytokines secretion, and these signaling cascades support NDV proliferation.

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eIF2α-CHOP-BCl-2/JNK and IRE1α-XBP1/JNK signaling promote apoptosis and inflammation and support the proliferation of Newcastle disease virus

In recent years, plasma-activated solutions (PASs) have made good progress in the disinfection of medical devices, tooth whitening, and fruit preservation. In this study, we investigated the inactivation efficacy of Newcastle disease virus by PASs. Water, 0.9% NaCl, and 0.3% H2O2 were excited by plasma to obtain the corresponding solutions PAS(H2O), PAS(NaCl), and PAS(H2O2). The complete inactivation of virus after PAS treatment for 30 min was confirmed by the embryo lethality assay (ELA) and hemagglutination (HA) test. Scanning electron microscopy (SEM) results showed that the morphology of the viral particle changed under PAS treatments. The total protein concentration of virus decreased as measured by a Bradford protein assay due to PAS treatment. The nucleic acid integrity assay demonstrated that viral RNA degraded into smaller fragments. Moreover, the physicochemical properties of PASs, including the oxidation-reduction potential (ORP), electrical conductivity, and H2O2 concentration, and electron spin resonance spectra analysis indicated that reactive oxygen and nitrogen species play a major role in the virus inactivation. Therefore, the application of PASs, as an environmentally friendly method, would be a promising alternative strategy in poultry industries.IMPORTANCE Newcastle disease (ND), as an infectious viral disease of avian species, caused significant economic losses to domestic animal and poultry industries. The traditional chemical sanitizers, such as chlorine-based products, are associated with risks of by-product formation with carcinogenic effects and environmental pollution. On the basis of this, plasma-activated water as a green disinfection product is a promising alternative for applications in stock farming and sterilization in hospitals and public places. In this study, we explored the inactivation efficacy of different plasma-activated solutions (PASs) against ND virus (NDV) and the possible underlying mechanisms. Our results demonstrated that reactive oxygen and nitrogen species detected in PASs, including short-lived OH˙ and NO˙ and long-lived H2O2, changed the morphology, destroyed the RNA structure, and degraded the protein of the virus, consequently resulting in virus inactivation. These lay a foundation for the application of PASs to resolve the issues of public health and environmental sanitation.

Inactivation Efficacy of Nonthermal Plasma-Activated Solutions against Newcastle Disease Virus

Since the first rescue of a recombinant Newcastle disease virus (rNDV) in the late 1990s, many more rNDVs have been rescued by researchers around the world. Regardless of methodology, the main principle behind rescue of the virus has remained the same, i.e., the formation of a functional replication complex by simultaneously providing the full-length viral RNA and the viral NP, P and L proteins. However, different strategies have been reported for the insertion of the full-length genome into a suitable transcription vector, which remains the most challenging step of the rescue. Moreover, several systems have been published for provision of the DNA-dependent RNA polymerase, which is needed for transcription of viral RNA (vRNA) from the transfected plasmid DNA. The aim of this article is to consolidate all of the current cDNA assembly strategies and transcription systems used in rescue of rNDV in order to attain a better understanding of the advantages and disadvantages of each approach.

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Rescue of recombinant Newcastle disease virus: current cloning strategies and RNA polymerase provision systems

Summary

Avian paramyxoviruses (APMVs) have been reported from a wide variety of avian species around the world. Avian paramyxoviruses are economically significant because of the huge mortality and morbidity associated with it. Twelve different serotypes of APMV have been reported till date. Avian paramyxoviruses belong to the family Paramyxoviridae under genus Avulavirus. Newcastle disease virus (APMV-1) is the most characterized members among the APMV serotypes. Complete genome sequence of all twelve APMV serotypes has been published recently. In recent years, APMV-1 has attracted the virologists for its oncolytic activity and its use as a vaccine vector for both animals and humans. The recombinant APMV-based vaccine offers a pertinent choice for the construction of live attenuated vaccine due to its minimum recombination frequency, modular nature of transcription and lack of DNA phase during its replication. Although insufficient data are available regarding other APMV serotypes, our understanding about the APMV biology is expanding rapidly because of the availability of modern molecular biology tools and high-throughput complete genome sequencing.

Sugandha Sinha

Papers

Newcastle disease virus: current status and our understanding