ABSTRACT Through comparative analysis, different coronaviruses, including the novel SARS-CoV-2 and human seasonal coronaviruses hCoV-OC43 and hCoV-NL63 will be used to unveil both their similarities and differences in cellular susceptibility and permissiveness, innate immune responses, and immune modulatory potential in primary human cell systems including monocyte derived dendritic cells (MDDCs), normal human bronchial epithelial cells (NHBEs), and an ex vivo tonsil histoculture (HC) system. We will use state of the art techniques to analyze tose responses intracellularly and extracellularly. Our group specializes in the manipulation of primary human cell systems and investigating both innate immune responses to viral infection as well as viral antagonism of innate immune sensing. As such we are uniquely positioned to respond to this new public health threat and provide critical information regarding the molecular biology of SARS-CoV-2.