Transcriptional effects of SARS-CoV-2 E protein and altered BET function

BET proteins are chromatin adaptors involved in gene transcription control, which recently were reported to interact with the SARS-CoV-2 envelope (E) protein, raising the question of whether the interaction constitutes a hijacking mechanism of the virus in the host cell. To evaluate this possibility, we have compared the effects on cell transcriptome of E overexpression with those of BET inhibition by the JQ1 drug. We have found that effects are quite different, and specially in relation to gene categories related to natural immunity and the interferon response we find opposite effects, being E overexpression a strong inductor of these genes. We have also identified a C-terminal fragment of BET proteins interacting with E. However, co-expression of this fragment with E is not altering the main transcriptional effects of E alone on immunity-related genes. Overall design: We transfected hek293T cells with a plasmid expressing the SARS-CoV-2 E protein and compared the transcriptional changes produced with cells treated with the BET protein inhibitor JQ1, to observe whether the changes were similar or opposite. In addition, we also transfected HEK293T cells with the plasmid expressing the E protein together with a plasmid expressing the fraction of BET proteins with which it interacts to study whether the interaction inhibits the effect of E protein overexpression.