Viral Replication and Nucleic Acid – Protein Interactions
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Institut Pasteur
Dpt de Virologie
Bat. Duclaux, 1er étage
28, rue du Dr Roux
75015 Paris, France
Scientific Interest
Our team is studying HIV-1 and SARS-CoV-2 replication, using biochemical, cellular and genomic approaches. The identification and characterization of essential nucleic-acid /protein host-virus interactions should serve to propose new antiviral strategies. Two parameters of HIV-1 replication are studied, the tridimensional (3D) chromatin environment surrounding the integrated proviral genome and DNA topoisomerases present in infected cells. Studies are focused on the role of these parameters as regulators of viral expression, especially during latency phases. The 3D chromatin environment is studied using Chromosome Conformation Capture derived approaches, which allow us to map contacts between viral and human genomes (Moreau et al., 2018). DNA topoisomerases are studied as regulators of HIV-1 transcription. Recently, our team has discovered that DNA TOP1 represses HIV-1 basal transcription and that this repression depends on its interaction with a Guanine-quadruplex (G4) present in the viral promoter (Lista et al., in revision). We are now studying this transcriptional regulation mechanism and its impact on HIV replication and latency. Since April 2020, we are studying the interaction between SARS-CoV-2 Nsp3 protein and G4s. As observed with SARS-CoV, we have shown that the SARS Unique Domain (SUD) of SARS-CoV-2 Nsp3 interacts with DNA and RNA G4s. Interestingly, these interactions are disrupted by G4-ligands and some of them possess an antiviral activity. Present studies are focused on these molecules (European Patent 20 306 606.3) and the identification of the actual G4 targets of viral Nsp3. The absence of stable G4 in the SARS-CoV-2 genome leads us to hypothesize that SUD interacts with cellular RNA G4s and that these interactions contribute to the infection and/or inflammation processes. Our projects benefit of precious collaborations (R. Koszul, Y. Pommier, H. Munier-Lehmann, P. England, JL. Mergny, MP. Teulade-Fichou, J. Guillon, G. Pratviel) and fundings by the I. Pasteur, the ANRS, Sidaction and the ANR.
Our team is studying HIV-1 and SARS-CoV-2 replication, using biochemical, cellular and genomic approaches. The identification and characterization of essential nucleic-acid /protein host-virus interactions should serve to propose new antiviral strategies. Two parameters of HIV-1 replication are studied, the tridimensional (3D) chromatin environment surrounding the integrated proviral genome and DNA topoisomerases present in infected cells. Studies are focused on the role of these parameters as regulators of viral expression, especially during latency phases. The 3D chromatin environment is studied using Chromosome Conformation Capture derived approaches, which allow us to map contacts between viral and human genomes (Moreau et al., 2018). DNA topoisomerases are studied as regulators of HIV-1 transcription. Recently, our team has discovered that DNA TOP1 represses HIV-1 basal transcription and that this repression depends on its interaction with a Guanine-quadruplex (G4) present in the viral promoter (Lista et al., in revision). We are now studying this transcriptional regulation mechanism and its impact on HIV replication and latency. Since April 2020, we are studying the interaction between SARS-CoV-2 Nsp3 protein and G4s. As observed with SARS-CoV, we have shown that the SARS Unique Domain (SUD) of SARS-CoV-2 Nsp3 interacts with DNA and RNA G4s. Interestingly, these interactions are disrupted by G4-ligands and some of them possess an antiviral activity. Present studies are focused on these molecules (European Patent 20 306 606.3) and the identification of the actual G4 targets of viral Nsp3. The absence of stable G4 in the SARS-CoV-2 genome leads us to hypothesize that SUD interacts with cellular RNA G4s and that these interactions contribute to the infection and/or inflammation processes. Our projects benefit of precious collaborations (R. Koszul, Y. Pommier, H. Munier-Lehmann, P. England, JL. Mergny, MP. Teulade-Fichou, J. Guillon, G. Pratviel) and fundings by the I. Pasteur, the ANRS, Sidaction and the ANR.
Thematic