Proteomic comparison of Marburg and Kasokero virus infection in natural host Egyptian rousette bat reveals distinct antiviral pathways

Bats are natural reservoir hosts for numerous zoonotic viruses, yet the molecular mechanisms enabling viral persistence without overt disease remain incompletely understood. The Egyptian rousette bat (Rousettus aegyptiacus, ERB) is the sole known natural reservoir of Marburg virus (MARV) and a key host in the enzootic cycle of the tick-borne Kasokero virus (KASV), providing a unique system to compare host responses to different RNA viruses within the same species. Here, we applied serial cross-sectional serum proteomics integrated with tissue-specific viral kinetics to characterize systemic host responses to experimental MARV and KASV infection in captive-reared bats. Nearly 16 % of detected proteins (67/419) were found exclusively in infected animals, yet canonical acute inflammatory signatures driving pathology in other susceptible hosts were absent (e.g., in humans and non-human primates). Differential abundance and detection analyses identified both shared and virus-dependent responses, with MARV infection eliciting limited and transient perturbations, while KASV induced broader and more sustained engagement of complement, lectin pathway, and hepatometabolic proteins. Network-based analysis uncovered coordinated proteasome modules, including circulating immunoproteasome complexes, consistent with enhanced antigen-processing capacity is a feature of these virus-host dynamics. Together, these findings reveal how ERBs mount structured, virus-dependent systemic responses, offering new insight into mechanisms underlying viral infection in natural reservoir hosts.