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Dr. Neufeldt obtained his BSc in immunology and PhD in Cell Biology from the University of Alberta working on how hepatitis C virus infection alters host nuclear transport pathways. Following his PhD, he moved to the University of Heidelberg in Germany where he continued his training in Molecular Virology in the laboratory of Ralf Bartenschlager. During this time, his research focused on characterizing flavivirus interactions with host membranes proteins. In 2021, Dr. Neufeldt joined the Emory faculty as an assistant professor in Microbiology and Immunology. Research in the Neufeldt lab uses integrated imaging techniques in combination with a range of molecular virology and cell biology tools to interrogate how positive-strand RNA virus infection manipulates cellular membrane systems to facilitate viral processes and limit immune activation.
SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB
SARS-CoV-2 is a novel virus that has rapidly spread, causing a global pandemic. In the majority of infected patients, SARS-CoV-2 leads to mild disease; however, in a significant proportion of infections, individuals develop severe symptoms that can lead to long-lasting lung damage or death. These severe cases are often associated with high levels of pro-inflammatory cytokines and low antiviral responses, which can cause systemic complications. Here, we have evaluated transcriptional and cytokine secretion profiles and detected a distinct upregulation of inflammatory cytokines in infected cell cultures and samples taken from infected patients. Building on these observations, we found a specific activation of NF-κB and a block of IRF3 nuclear translocation in SARS-CoV-2 infected cells. This NF-κB response was mediated by cGAS-STING activation and could be attenuated through several STING-targeting drugs. Our results show that SARS-CoV-2 directs a cGAS-STING mediated, NF-κB-driven inflammatory immune response in human epithelial cells that likely contributes to inflammatory responses seen in patients and could be therapeutically targeted to suppress severe disease symptoms.