SARS-CoV-2 restriction by the APOBEC3 innate immune effectors


Student thesis: Master typesMaster en biochimie et biologie moléculaire et cellulaire à finalité approfondie


SARS-CoV-2 is an emergent human Coronaviridae, responsible for the COVID-19. It is an enveloped positive sense single-stranded RNA virus. Like other RNA viruses, the SARS-CoV-2 evolves rapidly by accumulating mutations. Interestingly, those mutations are biased towards C-to-U transitions. This signature has been attributed to the catalytic activity of the APOBEC3 restriction factors. The APOBEC3 family is a group of seven cytidine deaminases that restrict viruses by mutating their genome. The goal of this project was to test whether one or several members of the APOBEC3 family can indeed restrict SARS-CoV-2 replication. Preliminary data lead us to focus on three candidates: APOBEC3A, APOBEC3H and APOBEC3G. Messenger RNA quantification of our candidates in nasopharyngeal swabs of infected patients showed an upregulation of APOBEC3A mRNA upon infection, upregulation that is positively-correlated with the viral load. The A549-ACE2 and Vero E6 cells, that are permissive for SARS-CoV-2 replication, were transduced to overexpress the APOBEC3A, APOBEC3H, APOBEC3G and APOBEC3GT218A (a mutant that cannot be phosphorylated in the residue T-218 and therefore cannot be enzymatically inactivated through phosphorylation) proteins. We observed that the viral replication was strongly reduced in cells expressing the APOBEC3H and APOBEC3GT218A proteins. No change was observed in the cells expressing the APOBEC3A and APOBEC3G proteins. Taken together, these results suggest a restriction effect acting on SARS-CoV-2. Further studies will be required, notably to investigate the suspected antagonization mechanism of APOBEC3G through phosphorylation of its T-218 residue.
la date de réponse18 janv. 2023
langue originaleAnglais
L'institution diplômante
  • Universite de Namur
SuperviseurNicolas Gillet (Promoteur)

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