Dissecting essential roles of chicken interferon stimulated genes in the pathobiology of poultry viruses

Resumo

To initiate successful virus replication cycle, viruses have to breach a cascade of host cellular responses. Among these barriers, innate immune responses are most potent and independent to nature of pathogens. The objectives of this work are to define the interactions of chicken interferon stimulated genes (chISGs) with diverse poultry viruses that are of economic importance both in Brazil and UK. Our preliminary transcriptomic and expression analysis indicate that chlSGs are the most potent responses of the chicken infected with Marek's disease virus (MOV) indicating that chlSGs essentially mediate pathobiology of viruses. In this proposal, we will dissect the significance and breadths of chlSGs against poultry viruses using large-scale, genome-wide and high through put screen platforms. Specifically, we will simultaneously measure the temporal expression of ISGs that synergistically or antagonistically regulate specific virus replication using a pre-established lentivirus-based ISG library. We will combine this data with results gain through shRNA mediated silencing screening to catalogue chlSGs with broad-spectrum or virus specific chlSGs. These data will be integrated within mechanistic studies to provide an incredible rich data on how viruses interact with host immune responses, essentially contributed by ISGs. and the ways viruses have adapted to circumvent these responses. These experimentations will be performed with avian influenza virus, avian paramyxoviruses and Marek's disease virus in The Pirbright Institute, UK and with avian metapneumoviruses and infectious bursal disease virus in State University of Campinas, Brazil using homogeneous system in two laboratory settings. Finally, the gained information will be utilized to establish a cell line having profound favorable effects on the growth kinetics. (AU)