ABSTRACT
Characteristic clinical manifestations of Newcastle disease include leukopenia and immunosuppression. Peripheral blood mononuclear cells (PBMCs) are the main targets of Newcastle disease virus (NDV) infection. To survey changes in proteomic expression in chicken PBMCs following NDV infection, PBMC proteins from 30 chickens were separated using two-dimensional electrophoresis (2-DE) and subjected to mass spectrometry analysis. Quantitative intensity analysis showed that the expression of 78 proteins increased more than two-fold. Thirty-five proteins exhibited consistent changes in expression and 13 were identified as unique proteins by matrix assisted laser desorption ionization-time of flight mass spectrometer/mass spectrometer including three that were down-regulated and 10 that were up-regulated. These proteins were sorted into five groups based on function: macromolecular biosynthesis, cytoskeleton organization, metabolism, stress responses, and signal transduction. Furthermore, Western blot analysis confirmed the down-regulation of integrin-linked kinase expression and up-regulation of lamin A production. These data provide insight into the in vivo response of target cells to NDV infection at the molecular level. Additionally, results from this study have helped elucidate the molecular pathogenesis of NDV and may facilitate the development of new antiviral therapies as well as innovative diagnostic methods.
Subject(s)
Animals , Avian Proteins/genetics , Chickens , Gene Expression Regulation , Leukocytes, Mononuclear/enzymology , Newcastle Disease/genetics , Newcastle disease virus/physiology , Poultry Diseases/genetics , Proteome , Specific Pathogen-Free Organisms , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/veterinary , Tandem Mass Spectrometry/veterinaryABSTRACT
Cancer is a major cause of deaths in humans. Though there has been significant progress in cancer therapy, the limited efficacy and toxicities of current chemo- and radiotherapies have provided an impetus for the search of new therapeutics. A therapeutic approach, which uses viruses for the treatment of cancer termed, oncolytic virotherapy has recently emerged. Newcastle disease virus (NDV) is one such virus with an inherent oncolytic property. NDV causes a highly infectious disease in poultry worldwide. In humans it is reported to have oncolytic and immuno-stimulatory effects. It specifically replicates in tumour cells while sparing normal cells and cause oncolysis. For many years different strains of the NDV have been investigated for treatment of various human cancers. Recent advances in reverse genetics provided investigators the tools to produce recombinant NDV with improved oncolytic property.
Subject(s)
Animals , Apoptosis , Humans , Neoplasms/pathology , Neoplasms/therapy , Newcastle disease virus/genetics , Newcastle disease virus/physiology , Oncolytic Virotherapy/methods , Oncolytic Viruses/genetics , Oncolytic Viruses/physiologyABSTRACT
No presente trabalho, foi investigada a produçäo de interferon nos tecidos da placenta humana induzidos por diferentes vírus. A membrana amniótica mostrou ser mais eficiente produtora de interferon quando infectada pelo vírus da doença de Newcastle (NDV) que a membrana ou as vilosidades coriônicas. A irradiaçäo do NDV com a luz ultravioleta (UV) diminuiu sua capacidade indutora nos três tecidos placentários. Os níveis de interferon encontrados em culturas da membrana amniótica ou coriônica, induzidos por vírus para-influenza I (Sendai), foram muito diferentes, dependendo da placenta utilizada, tanto com o vírus vivo como o tratado com a UV. Quando vilosidades coriônicas foram infectadas com este vírus, näo foi encontrada atividade de IFN. Testes comparativos mostraram que o NDV é melhor indutor de interferon do que o vírus Sendai em membrana amniótica. Os vírus Sindbis e Oriboca (vivos ou inativados pela UV) näo induziram títulos mensuráveis de interferon em qualquer dos tecidos mencionados. Concluiu-se que o sistema NDV - membrana amniótica é o mais eficiente na induçäo de IFN e merece investigaçöes mais abrangentes