Amazing stuff! Why are bats capable of hosting so many viruses without getting sick? Why are bats so unique? Why do we still not know more about bats?
"There have been several major outbreaks of emerging viral diseases, including Hendra, Nipah, Marburg and Ebola virus diseases, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS)—as well as the current pandemic of coronavirus disease 2019 (COVID-19). Notably, all of these outbreaks have been linked to suspected zoonotic transmission of bat-borne viruses. Bats—the only flying mammal—display several additional features that are unique among mammals, such as a long lifespan relative to body size, a low rate of tumorigenesis and an exceptional ability to host viruses without presenting clinical disease. ... Recent studies suggest that 64 million years of adaptive evolution have shaped the host defence system of bats to balance defence and tolerance, which has resulted in a unique ability to act as an ideal reservoir host for viruses. ... Studying the mechanisms of immune tolerance in bats could lead to new approaches to improving human health. ... The ability of bats to harbour many viruses—and zoonotic coronaviruses in particular—may result from their ability to efficiently regulate host responses to infection, although species richness may also have a role ...
bats represent 1,423 of the more than 6,400 known species of mammal ...
Bats have been associated with infectious diseases for centuries. Their role in the transmission of rabies virus led Metchnikov to investigate fruit bat macrophages and their immune responses in 1909 ...
By contrast, infected bats show no or minimal signs of disease even when high viral titres are detected in tissues or sera, which suggests that they are tolerant of viral diseases ...
Humans express minimal baseline levels of type I interferons (IFNs), and they are highly inducible upon stimulation. By comparison, the black flying fox (Pteropus alecto) constitutively expresses some baseline IFNα, and many species of bats express several IFN-stimulated genes before stimulation. ... The kinetics of the IFN response in bats also differs from those of other mammals, with a faster decline phase for some bat interferon-stimulated genes. In addition, several antiviral genes ... are IFN-induced in bats but not in other mammals or have undergone selection pressure to potentially alter function, such as those encoding Mx proteins96 and APOBEC397 ...
In addition to the innate immune responses, recent studies have shed light on other mechanisms of bat host defence. Enhanced autophagy has a key role in the increased clearance of lyssavirus from bat cells, and is known to regulate immunity and mediate pathogen clearance. Bats express very high levels of heat-shock proteins, which confers upon bat cells the ability to survive at high temperature and high oxidative stress in vitro. ...
Both naturally infected and experimentally infected bats indicate tolerance of viral infection, even during a transient phase of high viral titres. ... This supports an immunological tolerance to RNA viruses in bats, particularly during the acute response. ..."
bats represent 1,423 of the more than 6,400 known species of mammal ...
Bats have been associated with infectious diseases for centuries. Their role in the transmission of rabies virus led Metchnikov to investigate fruit bat macrophages and their immune responses in 1909 ...
By contrast, infected bats show no or minimal signs of disease even when high viral titres are detected in tissues or sera, which suggests that they are tolerant of viral diseases ...
Humans express minimal baseline levels of type I interferons (IFNs), and they are highly inducible upon stimulation. By comparison, the black flying fox (Pteropus alecto) constitutively expresses some baseline IFNα, and many species of bats express several IFN-stimulated genes before stimulation. ... The kinetics of the IFN response in bats also differs from those of other mammals, with a faster decline phase for some bat interferon-stimulated genes. In addition, several antiviral genes ... are IFN-induced in bats but not in other mammals or have undergone selection pressure to potentially alter function, such as those encoding Mx proteins96 and APOBEC397 ...
In addition to the innate immune responses, recent studies have shed light on other mechanisms of bat host defence. Enhanced autophagy has a key role in the increased clearance of lyssavirus from bat cells, and is known to regulate immunity and mediate pathogen clearance. Bats express very high levels of heat-shock proteins, which confers upon bat cells the ability to survive at high temperature and high oxidative stress in vitro. ...
Both naturally infected and experimentally infected bats indicate tolerance of viral infection, even during a transient phase of high viral titres. ... This supports an immunological tolerance to RNA viruses in bats, particularly during the acute response. ..."
Bats show an excellent balance between enhanced host defence responses and immune tolerance through several mechanisms. Examples of enhanced host defences include constitutive expression of IFNs and interferon-stimulated genes (ISGs), increased expression of heat-shock proteins (HSPs), a higher base level expression of the efflux pump ABCB1 and enhanced autophagy. On the other hand, dampened STING and suppressed inflammasome pathways—such as dampened NLRP3, loss of PYHIN and downstream IL-1β—contribute to immune tolerance in bats.
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