Severe Acute Respiratory Syndrome Coronavirus 2 could exploit human transcription factors involved in Interferon-mediated response

Abstract

Background The novel SARS-CoV-2 causing the pandemic acute respiratory disease COVID-19 is considered a worldwide emergency since no vaccines or effective antiviral are still available. As virus are dependent on the host transcriptional factors (TFs) to express the viral genes, efforts are required to understand the molecular interplay between virus and host response. Methods By bioinformatic analysis, we investigated human TFs involved in viral transcription. In particular, we analyzed the key role of the TF induced by Interferon regulatory factors (IRFs) exploiting the way of antiviral response related to interferon antiviral cytokines released during an infection. We compared SARS-CoV-2 consensus sequence from Italian patients with sequences in Coronaviridae ViPR database, to identify elements and TF binding sites that were present uniquely in the Italian viral sequence.Results Several TFs were induced by IRFs, others were induced by IFN-stimulated gene factor 3 (ISGF3) and by un-phosphorylated ISGF3 that was found to promote the transcription of several viral open reading frame. These data shed light on SARS-CoV2 dependence from the host transcription machinery associated to interferon-related antiviral response. We found binding sites for 11 TF present only in sequence of virus infecting humans and among these IRF8, IRF4, GLIS2, POU4F2 that were expressed in response to the viral infection and induced by interferon. POU4F2 binds in ORF1ab promoter; IRF8, and IRF4 both bind within the ORF1ab gene.Conclusions Our data suggest that SARS-CoV-2 can exploit the interferon-related host response, inducing the expression of genes by host TF involved in the regulation of transcription by RNA polymerase II, thus facilitating its own replication cycle.These data strengthen our knowledge about the transcription and replicative activity of the virus and could pave the way for new targets drug design.