The interplay between viruses and the immune system of bats

Abstract

Bats are an abundant and diverse group of mammals with an array of unique characteristics, including their well-known roles as natural reservoirs for a variety of viruses. These include the deadly zoonotic paramyxoviruses; Hendra (HeV) and Nipah (NiV)1,2, lyssaviruses3, coronaviruses such as severe acute respiratory coronavirus (SARS-CoV)4 and filoviruses such as Marburg5. Although these viruses are highly pathogenic in other species, including humans, bats rarely show clinical signs of disease whilst maintaining the ability to transmit virus to susceptible vertebrate hosts. In addition, bats are capable of clearing experimental infections with henipaviruses, filoviruses and lyssaviruses at doses of infection that are lethal in other mammals6–12. Curiously, the ability of bats to tolerate viral infections does not appear to extend to extracellular pathogens such as bacteria, fungi and parasites13. Over the past few years, considerable headway has been made into elucidating the mechanisms responsible for the ability of bats to control viral replication, with evidence for unique differences in the innate immune responses of bats14–20. However, many questions remain around mechanisms responsible for the ability of bats to co-exist with viruses, including their ability to tolerate constitutive immune activation, the triggers associated with viral spillover events and the sites of viral replication. Although bats appear to have all of the major components of the immune system present in other species, their unique ecological characteristics (including flight, high density populations and migration) combined with their long co-evolutionary history with viruses has likely shaped their immune response resulting in an equilibrium between the host and its pathogens.