Tools to study pathogen-host interactions in bats

Abstract

Bats are natural reservoirs for a variety of emerging viruses that cause significant disease in humans and domestic animals yet rarely cause clinical disease in bats. The co-evolutionary history of bats with viruses has been hypothesized to have shaped the bat-virus relationship, allowing both to exist in equilibrium. Progress in understanding bat-virus interactions and the isolation of bat-borne viruses has been accelerated in recent years by the development of susceptible bat cell lines. Viral sequences similar to severe acute respiratory syndrome corona virus (SARS-CoV) have been detected in bats, and filoviruses such as Marburg virus have been isolated from bats, providing definitive evidence for the role of bats as the natural host reservoir. Although viruses can be readily detected in bats using molecular approaches, virus isolation is far more challenging. One of the limitations in using traditional culture systems from non-reservoir species is that cell types and culture conditions may not be compatible for isolation of bat-borne viruses. There is, therefore, a need to develop additional bat cell lines that correspond to different cell types, including less represented cell types such as immune cells, and culture them under more physiologically relevant conditions to study virus host interactions and for virus isolation. In this review, we highlight the current progress in understanding bat-virus interactions in bat cell line systems and some of the challenges and limitations associated with cell lines. Future directions to address some of these challenges to better understand host-pathogen interactions in these intriguing mammals are also discussed, not only in relation to viruses but also other pathogens carried by bats including bacteria and fungi.

Keywords: Bats; Cell lines; Chiroptera; Host-pathogen interaction; Viral reservoirs; Virus isolation.

Fig. 1

There is a need to develop more model cell lines and animal models to decipher the immune responses of bats to viruses. Viruses display tropism towards different cell types and there is a need to generate cell lines representative of the multitude of cell types found in bats to increase the chances of isolating the viruses that they carry. Alternatively, genetically modified cell lines can be generated that do not express antiviral interferons from these cell types for virus isolation. These cells may be used to propagate bat-borne viruses to high titres for ex vivo, in vitro and in vivo experiments. Generating cell lines from a variety of different tissues and bats will allow researchers to explore virus susceptibility and virus-host interactions in these intriguing mammals. Generation of outbred (wild-caught) and inbred (laboratory bred) bat colonies with known infection status will enable systemic immune response studies with relevant viruses isolated from bats. The ability to resist infections with some of these viruses may be an effect of several evolutionary adaptations, which can be better dissected by studying the systemic responses in bats.