Investigate the immune modulation function of SARS-CoV-2 accessory protein ORF8

The COVID-19 pandemic has been caused by the highly pathogenic human coronavirus SARS-CoV-2. In addition to the heavy death toll of more than 6 million lives, COVID-19 has disrupted virtually every aspect of social life, and led to astronomical loss in economy. The hallmark of severe COVID-19 disease is the acute respiratory distress syndrome (ARDS) associated with dysregulated immune responses. Human immune system often mounts sequential and regulated innate and adaptive immune responses upon viral infections, which are turned off with infections resolved, thus restoring immune homeostasis. However, SARS-CoV-2 infection has been shown to suppress antiviral interferon response while increase production of proinflammatory cytokines, disrupt the balance of various immune cell subtypes, damage immune cell functions including the antibody dependent cellular cytotoxicity (ADCC) activity. These impacts together cultimate in the detrimental immunopathology seen in severely ill COVID-19 patients. Unfortunately, it is largely unclear how SARS-CoV-2 deteriorates host immune functions, which makes it difficult to develop targeted approaches to restore effective antiviral responses, and cure SARS-CoV-2 infection. The goal of our study is to demonstrate that SARS-CoV-2 exerts systemic effect on host immune cells through its secreted protein ORF8 which is able to act on multiple key immune cells types by interacting with the cell surface Fc receptors and disrupting crucial antiviral immune functions including ADCC. Our study is expected not only to promote the discovery of new therapeutics and prevention strategies to manage SARS-CoV-2 infection, but also to advance our knowledge of coronavirus biology and prepare for future new coronavirus outbreaks and pandemics.