Innate signaling pathways can regulate influenza virus replication, and there are viral countermeasures, but there remain critical gaps in our knowledge about how these responses impact viral disease pathogenesis. The overarching goal of this highly integrated program is to systematically address these questions using a systems-based approach to reveal new therapeutic approaches. The goal of the Genomics Core is to provide a central resource that will facilitate high throughput sequencing of the transcriptome (mRNA-seq, GRO-Seq, and Nanostring gene expression analysis) and the epigenome (ChlP-Seq) in influenza virus infected cells. The core will also provide data analysis and integrafion to uncover the virus-host transcriptional response network. This information will be used by other program investigators in the Modeling Core to define host molecular networks and pathways that impact influenza virus infection and to define rare and disruptive gene polymorphisms that influence influenza virus disease pathogenesis (Project 3). Cellular networks, pathways, and genes that are implicated in the virus-host transcriptional response network will be targeted by RNAi-knockdown to determine how perturbations in the system impact the transcriptional response network to infection by wild-type and specific mutant influenza A viruses. These studies are critical for the overall goal ofthe program aimed at uncovering the global effects of influenza virus on cellular functions and on the system of key antiviral responses and virus countermeasures.
The goal of this proposal is to understand the host antiviral responses to influenza virus infection and to reveal the molecular mechanisms associated with virus countermeasures. The Genomics Core will conduct high throughput transcriptome and epigenome sequencing and data analysis to identify components of the influenza virus-host transcriptional response network. These studies will provide new insights into influenza virus-host interactions and should lead to new therapeutic strategies...
|Morris, John H; Knudsen, Giselle M; Verschueren, Erik et al. (2014) Affinity purification-mass spectrometry and network analysis to understand protein-protein interactions. Nat Protoc 9:2539-54|
|Rajsbaum, Ricardo; Versteeg, Gijs A; Schmid, Sonja et al. (2014) Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKK? kinase-mediated antiviral response. Immunity 40:880-95|
|Rajsbaum, Ricardo; Garcia-Sastre, Adolfo; Versteeg, Gijs A (2014) TRIMmunity: the roles of the TRIM E3-ubiquitin ligase family in innate antiviral immunity. J Mol Biol 426:1265-84|
|Schotsaert, Michael; García-Sastre, Adolfo (2014) Influenza vaccines: a moving interdisciplinary field. Viruses 6:3809-26|