tetano
Editor, Senior Moderator
Cell Rep
. 2023 Nov 21;42(12):113478.
doi: 10.1016/j.celrep.2023.113478. Online ahead of print. Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53
Jonathan D Lee[SUP] 1 [/SUP], Bridget L Menasche[SUP] 2 [/SUP], Maria Mavrikaki[SUP] 3 [/SUP], Madison M Uyemura[SUP] 3 [/SUP], Su Min Hong[SUP] 4 [/SUP], Nina Kozlova[SUP] 4 [/SUP], Jin Wei[SUP] 2 [/SUP], Mia M Alfajaro[SUP] 2 [/SUP], Renata B Filler[SUP] 2 [/SUP], Arne Müller[SUP] 3 [/SUP], Tanvi Saxena[SUP] 3 [/SUP], Ryan R Posey[SUP] 5 [/SUP], Priscilla Cheung[SUP] 6 [/SUP], Taru Muranen[SUP] 4 [/SUP], Yujing J Heng[SUP] 3 [/SUP], Joao A Paulo[SUP] 7 [/SUP], Craig B Wilen[SUP] 2 [/SUP], Frank J Slack[SUP] 8 [/SUP]
Affiliations
Coronavirus disease 2019 (COVID-19) remains a significant public health threat due to the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and Middle East respiratory syndrome (MERS)-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here, we use our recently developed integrative DNA And Protein Tagging methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants.
Keywords: ATAC-seq; COVID-19; CP: Immunology; SARS-CoV-2; chromatin; iDAPT-MS; p53; proteomics; senescence; spike.
. 2023 Nov 21;42(12):113478.
doi: 10.1016/j.celrep.2023.113478. Online ahead of print. Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53
Jonathan D Lee[SUP] 1 [/SUP], Bridget L Menasche[SUP] 2 [/SUP], Maria Mavrikaki[SUP] 3 [/SUP], Madison M Uyemura[SUP] 3 [/SUP], Su Min Hong[SUP] 4 [/SUP], Nina Kozlova[SUP] 4 [/SUP], Jin Wei[SUP] 2 [/SUP], Mia M Alfajaro[SUP] 2 [/SUP], Renata B Filler[SUP] 2 [/SUP], Arne Müller[SUP] 3 [/SUP], Tanvi Saxena[SUP] 3 [/SUP], Ryan R Posey[SUP] 5 [/SUP], Priscilla Cheung[SUP] 6 [/SUP], Taru Muranen[SUP] 4 [/SUP], Yujing J Heng[SUP] 3 [/SUP], Joao A Paulo[SUP] 7 [/SUP], Craig B Wilen[SUP] 2 [/SUP], Frank J Slack[SUP] 8 [/SUP]
Affiliations
- PMID: 37991919
- DOI: 10.1016/j.celrep.2023.113478
Coronavirus disease 2019 (COVID-19) remains a significant public health threat due to the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and Middle East respiratory syndrome (MERS)-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here, we use our recently developed integrative DNA And Protein Tagging methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses. SARS-CoV-2 infection induces TP53 stabilization on chromatin, which contributes to its host cytopathic effect. We mapped this TP53 stabilization to the SARS-CoV-2 spike and its propensity to form syncytia, a consequence of cell-cell fusion. Differences in SARS-CoV-2 spike variant-induced syncytia formation modify chromatin accessibility, cellular senescence, and inflammatory cytokine release via TP53. Our findings suggest that differences in syncytia formation alter senescence-associated inflammation, which varies among SARS-CoV-2 variants.
Keywords: ATAC-seq; COVID-19; CP: Immunology; SARS-CoV-2; chromatin; iDAPT-MS; p53; proteomics; senescence; spike.