Functional impact of Regulatory RNAs in EBOLA virus infected macrophages 4747

Abstract Description Most of the human transcriptome is made up of non-coding RNAs, which regulate the expression and function of protein-coding genes, influencing immune cell development, differentiation, and response to pathogens. Infections induce global changes in regulatory non-coding RNA (ncRNA) expression, and it is believed that pathogens impact immune cell functions through the differential induction of regulatory ncRNAs. The Ebola virus (EBOV), a causative agent of severe disease in affected individuals, primarily targets macrophages. The virus’s extraordinary pathogenicity is due to its ability to infect cells efficiently and, at the same time, to suppress immune responses at early time points of replication. However, the impact of ncRNAs on EBOV replication and the immune response of human macrophages to the infection has not been studied. Our data show that an EBOV-induced long non-coding RNA (lncRNA) regulates a transcription factor, ATF3, which orchestrates a variety of signaling pathways. Our results suggest that host lncRNAs in EBOV-infected macrophages orchestrate an immune response to infection and potentially play a role in pathogenesis. In addition, our analyses show several EBOV-suppressed ncRNAs can potentially antagonize the virus directly. Our studies may discover novel regulatory mechanisms and host proteins and ncRNAs to target with novel therapies to combat the viral disease. Funding Sources R01AI157850 Texas Biomedical Institute Forum grant 2024 Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)