PNNL

Abstract

The broad range and diversity of interferon stimulated genes (ISGs) function to induce an antiviral state within the host, impeding viral pathogenesis. While successful respiratory viruses overcome individual ISG effectors, analysis of the global ISG response and subsequent viral antagonism has yet to be examined. Employing models of the human airway, transcriptomics and proteomics datasets were used to compare ISG response patterns following highly pathogenic H5N1 avian (HPAI) influenza A virus, 2009 pandemic H1N1, SARS-Coronavirus (CoV), and MERS-CoV infection. The results illustrated distinct approaches utilized by each virus to antagonize the global ISG response. Further examination revealed that delayed interferon induction contributes to CoV antagonism. In addition, the data revealed that highly virulent HPAI virus and MERS-CoV induce repressive histone modifications, which down regulate expression of subsets of ISGs. Notably, influenza A virus NS1 appears to play a central role in this histone mediated down regulation in highly pathogenic influenza strains. Together, the work demonstrates the existence of unique and common viral strategies for controlling the global ISG response and provides a novel avenue for viral antagonism via altered histone modification.