Impact of the APOBEC3 innate immune effectors on SARS-CoV-2 replication

  • Maxence Collard

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


    APOBEC proteins are a family of effectors of our immune system. They catalyze the deamination of cytosine into uracil on single-stranded nucleic acids. This activity allows them to introduce mutations into the genome of viruses and retroelements. When a high number of mutations are induced, it impairs the production of an infectious progeny. In addition to these deamination-dependent effects, APOBEC proteins can bind to viral elements involved in their life cycle. This capacity alters the proper replication of viruses. Obviously, viruses have coevolved with defense mechanisms and developed many ways to protect themselves from the actions of the deaminases. The long coexistence between viruses and APOBEC proteins has left footprints and shaped viral evolution.
    SARS-CoV-2, the virus responsible for the global outbreak of COVID-19, has been massively analyzed. Due to the magnitude of the pandemic, a huge amount of data was collected. Through these investigations, several authors have identified biases in the distribution of nucleotides. This includes a strong transition of cytosine into uracil. This observation leads us to believe that APOBEC proteins may be involved in SARS-CoV-2 restriction.
    Based on these observations, we chose to study the impact of APOBEC proteins on SARS-CoV-2 replication. We constructed different cell lines overexpressing different APOBEC proteins and infected them with SARS-CoV-2 to investigate whether the APOBEC proteins could effectively limit (or promote) SARS-CoV-2 replication. We were not able to observe any difference in the SARS-CoV-2 replication kinetics between cell lines overexpressing APOBEC proteins and those not overexpressing them. In order to guide us on which APOBEC3 would be most relevant to study in the context of SARS-CoV-2 replication, we decided to study their expression profile in primary human bronchial cells infected with SARS-CoV-2. We compared infected cells with uninfected cells and it turned out that the expression of APOBEC3G is particularly upregulated at the mRNA and protein levels. We could not observe any increased deamination activity in the infected cells despite an increase of APOBEC3G protein level. This raises the possibility that the virus can inhibit the deaminase activity of the APOBEC3G protein.
    la date de réponsejanv. 2022
    langue originaleAnglais
    L'institution diplômante
    • Universite de Namur
    SuperviseurNicolas Gillet (Promoteur) & Kevin Willemart (Copromoteur)

    Contient cette citation