Systems approaches to Coronavirus pathogenesis.
Coronaviruses comprise a large group of emergent human and animal pathogens, including the highly pathogenic SARS-CoV and MERS-CoV strains that cause significant morbidity and mortality in infected individuals, especially the elderly. As emergent viruses may cause episodic outbreaks of disease over time, human samples are limited. Systems biology and genetic technologies maximize opportunities for identifying critical host and viral genetic factors that regulate susceptibility and virus-induced disease severity. These approaches provide discovery platforms that highlight and allow targeted confirmation of critical targets for prophylactics and therapeutics, especially critical in an outbreak setting. Although poorly understood, it has long been recognized that host regulation of virus-associated disease severity is multigenic. The advent of systems genetic and biology resources provides new opportunities for deconvoluting the complex genetic interactions and expression networks that regulate pathogenic or protective host response patterns following virus infection. Using SARS-CoV as a model, dynamic transcriptional network changes and disease-associated phenotypes have been identified in different genetic backgrounds, leading to the promise of population-wide discovery of the underpinnings of Coronavirus pathogenesis.
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, United States.
Alexandra
A
Schäfer
Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, United States.
Ralph S
RS
Baric
Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, United States. Electronic address: mtferris@unc.edu.
Martin T
MT
Ferris
D000818:Animals; D017934:Coronavirus / Q000502:physiology*; D018352:Coronavirus Infections / Q000209:etiology* / Q000821:virology; D005821:Genetic Techniques; D005823:Genetics; D054884:Host-Pathogen Interactions; D006801:Humans; D049490:Systems Biology / Q000379:methods