INNATE IMMUNE DEFENCES AGAINST SARS COV-2 AND VIRAL COUNTERMEASURES

Abstract

SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has infected more than 22 million people around the globe. Although this pandemic pathogen spreads with enormous efficiency it seems to be highly sensitive to interferons. Here, I will discuss some of the mechanisms allowing SARS CoV-2 to prevent control by the innate immune response and to escape or even highjack specific cellular antiviral factors. In collaborative studies, we found that the non-structural protein 1 (Nsp1) of SARS CoV-2 targets ribosomes to shutdown cellular mRNA translation and consequently the antiviral immune response. I will show that the Zinc finger antiviral protein (ZAP) that specifically targets CpG dinucleotides in viral RNA sequences restricts SARS-CoV-2, although this pandemic pathogen emerged from zoonosis of a coronavirus that was preadapted to the low CpG environment in humans. Finally, I will provide evidence that SARS CoV-2 may actually highjack specific “antiviral” factor for efficient infection of human lung cells.