A systems biology approach unveils different gene expression control mechanisms governing the immune response genetic program in peripheral blood mononuclear cells exposed to SARS-CoV-2

Abstract

COVID-19 and other pandemic viruses continue being important for public health and the global economy. Therefore, it is essential to explore the pathogenesis of COVID-19 more deeply, particularly its association with inflammatory and antiviral processes. In this study, we used the RNA-seq technique to analyze mRNA and non-coding RNA profiles of human peripheral blood mononuclear cells (PBMCs) from healthy individuals after SARS-CoV-2 in vitro exposure, to identify pathways related to immune response and the regulatory post-transcriptional mechanisms triggered that can serve as possible complementary therapeutic targets. Our analyses show that SARS-CoV-2 induced a significant regulation in the expression of 790 genes in PBMCs, of which 733 correspond to mRNAs and 57 to non-coding RNAs (lncRNAs). The immune response, antiviral response, signaling, cell proliferation and metabolism are the main biological processes involved. Among these, the inflammatory response groups the majority of regulated genes with an increase in the expression of chemokines involved in the recruitment of monocytes, neutrophils and T-cells. Additionally, it was observed that exposure to SARS-CoV-2 induces the expression of genes related to the IL-27 pathway but not of IFN-I or IFN-III, indicating the induction of ISGs through this pathway rather than the IFN genes. Moreover, several lncRNA and RNA binding proteins that can act in the cis-regulation of genes of the IL-27 pathway were identified. Our results indicate that SARS-CoV-2 can regulate the expression of multiple genes in PBMCs, mainly related to the inflammatory and antiviral response. Among these, lncRNAs establish an important mechanism in regulating the immune response to the virus. They could contribute to developing severe forms of COVID-19, constituting a possible therapeutic target.