Marburg and Sudan viruses elicit divergent interferon responses and cytokine storm signaling in Egyptian rousette bat macrophages

Introduction Egyptian rousette bats (ERBs) are the only known natural reservoir of Marburg virus (MARV), etiologic agent of a highly-pathogenic zoonotic viral hemorrhagic fever. Evolutionary adaptations in ERBs allow for fine-tuned discrete pro-inflammatory immune responses that control MARV infection, yet permit population-level viral maintenance. Methods To look for exclusive co-adapted responses between ERBs and MARV, we compared macrophage (MΦ) responses to MARV and Sudan virus (SUDV), a related filovirus not hosted by ERBs. We queried whether MARV counters normal ERB MΦ 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. Results We observed stark differences in MΦ 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 MΦs undergo muted IFN responses and cytokine storm signaling, SUDV induces unperturbed type I and III IFN gene expression, stronger cytokine and chemokine responses resembling typical host responses to a foreign viral pathogen. Discussion Our findings corroborate growing evidence of unique coevolutionary relationships between bats and the specific viruses they harbor.