Egyptian rousette bat macrophages elicit divergent interferon responses and cytokine storm signalling against Marburg and Sudan viruses

Egyptian rousette bats (ERBs) are the only known natural reservoir of Marburg virus (MARV), etiologic agent of a highly-pathogenic zoonotic viral hemorrhagic fever. In ERBs, evolutionary adaptations allow for fine-tuned discrete pro-inflammatory immune responses that control MARV infection, yet permit population-level viral maintenance. To look for exclusive co-adapted responses between ERBs and MARV, we compared macrophage (M{Phi}) responses to MARV and Sudan virus (SUDV), a related filovirus not hosted by ERBs. We queried whether MARV counters normal ERB M{Phi} responses, illuminating co-adapted host responses not observed upon infection with SUDV, which fails to establish a productive infection and is efficiently immunologically cleared by ERBs. We observed stark differences in M{Phi} transcriptional responses to MARV and SUDV, including differences in Type I and III interferon (IFN)-related genes, cytokines, chemokines, cell growth and proliferation genes. We show for the first time that while MARV-infected bat M{Phi}s undergo muted IFN responses and cytokine storm signalling, SUDV induces unperturbed Type I and III IFN gene expression, stronger cytokine and chemokine responses resembling typical host responses to a foreign viral pathogen. Our findings therefore corroborate growing evidence of unique coevolutionary relationships between bats and the specific viruses they harbor.