Role of proinflammatory cytokines, PML nuclear bodies, and the HIRA histone chaperone complex in epigenetic changes associated to SARS-CoV-2 infection – CHROMACoV

Cytokine storm is a hallmark of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19). As a consequence some patients could develop severe inflammatory diseases some of which leading to cardiac failure. Tumor Necrosis Factor alpha (TNF-a), High Mobility Group Box 1 (HMGB1) protein, and type I interferon (IFN-I) are major pro-inflammatory cytokines associated with COVID-19. Signaling pathways triggered by the cytokines end up in the nucleus modifying the transcriptome of the infected and non-infected cells through epigenetic regulation. Promyelocytic Leukemia (PML) Nuclear Bodies (NBs) are sensors of these signaling pathways, and together with the histone H3.3 variant HIRA chaperone complex, they contribute to the regulation of the expression of at least the IFN stimulated genes (ISGs). The CHROMACoV project proposes to decipher the impact of the TNF-a HMGB1, and IFN-I cytokines secretion together with the PML NBs/HIRA/H3.3 axis in the onset of the molecular and biological events leading to inflammatory complications associated to the COVID-19.