| First Author | Chen IP | Year | 2022 |
| Journal | Cell Rep | Volume | 40 |
| Issue | 3 | Pages | 111088 |
| PubMed ID | 35839775 | Mgi Jnum | J:331767 |
| Mgi Id | MGI:7326985 | Doi | 10.1016/j.celrep.2022.111088 |
| Citation | Chen IP, et al. (2022) Viral E protein neutralizes BET protein-mediated post-entry antagonism of SARS-CoV-2. Cell Rep 40(3):111088 |
| abstractText | Inhibitors of bromodomain and extraterminal domain (BET) proteins are possible anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prophylactics as they downregulate angiotensin-converting enzyme 2 (ACE2). Here we show that BET proteins should not be inactivated therapeutically because they are critical antiviral factors at the post-entry level. Depletion of BRD3 or BRD4 in cells overexpressing ACE2 exacerbates SARS-CoV-2 infection; the same is observed when cells with endogenous ACE2 expression are treated with BET inhibitors during infection and not before. Viral replication and mortality are also enhanced in BET inhibitor-treated mice overexpressing ACE2. BET inactivation suppresses interferon production induced by SARS-CoV-2, a process phenocopied by the envelope (E) protein previously identified as a possible "histone mimetic." E protein, in an acetylated form, directly binds the second bromodomain of BRD4. Our data support a model where SARS-CoV-2 E protein evolved to antagonize interferon responses via BET protein inhibition; this neutralization should not be further enhanced with BET inhibitor treatment. |
