Marburg and Kasokero viruses elicit differential antiviral innate immune control by their natural reservoir bat, the Egyptian rousette (Rousettus aegyptiacus)

Abstract

To investigate the antiviral innate immune responses of natural reservoir bats, we conducted a histopathological analysis of Egyptian rousettes (Rousettus aegyptiacus) experimentally infected with either of two divergent RNA viruses they naturally host, Marburg virus (MARV; family Filoviridae) and Kasokero virus (KASV; family Nairoviridae). Bats were serially euthanized at similar post-infection time points and tissue-based analyses focused on the liver, the primary target for both viruses. At 3 days post-infection (DPI), in situ hybridization (ISH) signal for replicating MARV was 300x less evident than that of KASV, with little immune cell recruitment and localized interferon (IFN)-stimulated responses suggesting a tendency towards superb virus replication control and non-cytolytic viral clearance. By comparison, an early burst of hepatocellular KASV replication correlated with robust, tissue-wide IFN-stimulated responses, mononuclear phagocyte apoptosis, targeted natural killer (NK) and/or natural killer T (NKT) cell responses and localized cytokine induction, demonstrating the capacity to swiftly establish an antiviral state. The distinctive lack of IFN stimulated gene 15 and MARV RNA hepatocellular co-localization in a single MARV-infected bat with overt hepatitis suggests a fine-tuned role for IFN antagonism in Egyptian rousettes, and hints at how MARV-IFN pathway interactions might influence the evolution, transmission and maintenance of orthomarburgviruses in nature, whereas KASV is less adaptable to this vertebrate host. This work augments our understanding of bat immunology and suggests certain co-evolutionary relationships between bats and viruses. These defenses may be more broadly applicable to other viruses circulating in Egyptian rousettes and likely to other bat-virus relationships.