Studying bats using a One Health lens: bridging the gap between bat virology and disease ecology

Abstract

Accumulating data suggest that some bat species host emerging viruses that are highly pathogenic in humans and agricultural animals. Laboratory-based studies have highlighted important adaptations in bat immune systems that allow them to better tolerate viral infections compared to humans. Simultaneously, ecological studies have discovered critical extrinsic factors, such as nutritional stress, that correlate with virus shedding in wild-caught bats. Despite some progress in independently understanding the role of bats as reservoirs of emerging viruses, there remains a significant gap in the molecular understanding of factors that drive virus spillover from bats. Driven by a collective goal of bridging the gap between the fields of bat virology, immunology, and disease ecology, we hosted a satellite symposium at the 2024 American Society for Virology meeting. Bringing together virologists, immunologists, and disease ecologists, we discussed the intrinsic and extrinsic factors such as virus receptor engagement, adaptive immunity, and virus ecology that influence spillover from bat hosts. This article summarizes the topics discussed during the symposium and emphasizes the need for interdisciplinary collaborations and resource sharing.

Keywords: ASV 2024; bats; disease ecology; immunity; satellite symposium; virology.

Fig 1

Studying bats using a One Health lens. (A) Some bat species are recognized as reservoir hosts of zoonotic viruses, including filoviruses, paramyxoviruses, and CoVs. The interaction of the CoV spike protein with cellular receptors is primarily mediated through the RBD. (1) Replication incompetent, vesicular stomatitis virus (VSV) pseudotyped viruses engineered with a generic CoV spike backbone and a replaceable RBD have been used to identify cellular receptors utilized by various sarbecoviruses and merbecoviruses. (2) Reverse genetics is an alternative approach to study the pathogenic potential of newly emergent viruses. Mühlberger et al. have developed this approach to generate infectious clones for LLOV, where a chimeric minigenome system complementing the missing genome ends of LLOV with the homologous regions from closely related filoviruses was used. LLOV isolates were used to evaluate virus replication in human and bat cell lines, along with the evaluation of pathogenicity in animal models. (B) Despite harboring viruses that are pathogenic in humans, infected bats do not show overt signs of disease. Research on bat immunity can help us understand the molecular factors that are involved in viral tolerance. One approach to studying bat immunity is the use of comparative genomic techniques and mechanistic characterization of cell signaling pathways and virus–host interactions. These approaches have demonstrated that some bat species have positively selected for genes within non-immune gene containing loci of their genomes to tolerate virus infections. The adaptation of new technologies to study bat immunology, such as scRNA-seq, has been critical for investigating immune cell populations without the need for cross-reactive reagents. (C) An important factor to prevent virus spillover from bats is understanding the intrinsic and extrinsic ecological factors that affect virus shedding in these mammals. Long-distance migration may function as a stressor for bats, as the energetic cost for undertaking such movements could weaken immune function. Migration occurs across bat families, and field studies that interrogate diverse metrics of glucocorticoid and immune activity across the annual cycle are needed to better understand how long-distance movements impact stress physiology, immune activity, and virus shedding in migratory bats. (D) Biosurveillance of bat populations is crucial for identifying and monitoring host species that may harbor pathogens. (3) Sero-surveillance, whether through detection of binding or neutralizing antibodies, can be a powerful tool for emerging zoonotic virus surveillance, circumventing challenges of detecting viral nucleic acid or virus isolates from sub-clinically infected wildlife hosts. Laing et al. have developed antigen-based multiplex serology assays to detect zoonotic viruses in bats, non-human animals, and humans and are constructing sero-epidemiology models to elucidate spillover drivers. (4) Accurate identification of host species is essential for effective biosurveillance. DNA barcoding is a common molecular method for species identification, involving voucher specimen which can additionally be used for the generation of cell lines for in vitro work. The accuracy of DNA barcoding can be enhanced by ancillary ecological data, such as echolocation calls.