Fc-effector functions against SARS-CoV-2: role of the viral accessory protein ORF8

SARS-CoV-2 is the etiological agent responsible for the COVID-19 pandemic that started in December 2019 and caused over 7 million deaths worldwide. Although vaccines were rapidly deployed and helped decrease disease severity, cases of reinfections are not rare as SARS-CoV-2 is likely to remain endemic. It is therefore critical to better understand the virus strategies to evade host immunity, elicited after vaccination or infection, to counterattack new Variants of Concern (VOCs) of SARS-CoV-2, limit reinfection cases and prevent possible future coronavirus outbreaks. One key player in host immune evasion is the viral accessory protein ORF8 that was reported to have unique ways of improving virus pathogenicity, was associated with the survival of infected cells and positively correlated with disease severity. Moreover, ORF8 was shown to decrease surface levels of Fc receptors on immune cells, which are crucial for activating immune responses and protecting the host. Furthermore, SARS-CoV-2 infected individuals were shown to have an impaired Natural Killer cell immunotype, leading to an overactivation or exhaustion of these important immune cells. We have generated evidence supporting a direct role of ORF8 on these phenotypes.