Computational approaches to understanding dendritic cell responses to influenza virus infection
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IMMUNOLOGY AT MOUNT SINAI
Computational approaches to understanding dendritic cell responses to influenza virus infection Elena Zaslavsky • Fernand Hayot • Stuart C. Sealfon
Stuart C. Sealfon Ó Springer Science+Business Media, LLC 2012
Abstract The evolution of immunology research from measurements of single entities to large-scale data-intensive assays necessitates the integration of experimental work with bioinformatics and computational approaches. The introduction of physics into immunology has led to the study of new phenomena, such as cellular noise, which is likely to prove increasingly important to understand immune system responses. The fusion of ‘‘hard science’’ and biology is also leading to a re-examination of data acquisition, analysis, and statistical validation and is resulting in the development of easy-toaccess tools for immunology research. Here, we review some of our models, computational tools, and results related to studies of the innate immune response of human dendritic cells to viral infection. Our project functions on an open model across institutions with electronic record keeping and public sharing of data. Our tools, models, and data can be accessed at http://tsb.mssm.edu/primeportal/. Keywords
Computational immunology Tools Models Dendritic cells
Project We have undertaken an NIAID-sponsored Modeling Immunity for biodefense project that involves a tight collaboration between experimenters and modelers. The aim is to develop a mechanistic understanding of the initial stages of viral infection, in order to be able to comprehend and predict pathogenicity of newly emerging viruses. We focus on the innate immune response in dendritic cells (DCs). DCs, as professional antigen presenting cells, contribute to the development of the adaptive immune response tailored to each specific virus [1]. For the in vitro component of our experimental work, the DCs studied are derived from monocytes extracted from human blood. The interaction between viruses and DCs is a complicated dance, where the cells attempt to limit the impact of the virus and the virus
E. Zaslavsky F. Hayot S. C. Sealfon (&) Department of Neurology and Center for Translational Systems Biology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6574, USA e-mail: [email protected]
attempts to circumvent cellular defenses. The viruses studied are the Newcastle disease virus (NDV) and H1N1 influenza A viruses. NDV, because it is avian, does not counteract the cellular immune response in human DCs, thus allowing a full view of the temporal development of that response [2]. Influenza A H1N1 viruses studied range from PR8 to the 1918 pandemic virus, including seasonal viruses such as Texas/91, New Caledonia/99, and the recent pandemic virus Cal/09, as well as sequence modified viruses to alter their immune antagonists or to incorporate fluorescent reporter proteins. These viruses interfere with the immune responses at many different levels once they have entered the cell [3]. A comparison of
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