Ebola, rabies, SARS, Nipah, and MERS-CoV all have something in common. They are all viruses, spread by bats, that often cause lethal disease in humans—the 2014-2015 Ebola outbreak killed over 11,000 people1—yet they don't sicken or kill their bat hosts. When animals efficiently transmits disease for long periods of time in the absence of disease themselves, they are known as reservoirs.

So what is it about bats that allow them to act as reservoirs for over 60 human pathogens? This question has plagued the scientific community for decades, starting with the discovery of bats as the reservoir for rabies virus in 1932 and continuing today with the recent Ebola outbreak and the ongoing search for novel viruses that may cause the next pandemic2. Part of my work focuses on this – digging in to the genome of these new viruses to investigate how closely related they may be to known viruses that infect humans.

A number of lifestyle factors make bats unique which may help explain their seeming resistance to pathogens causing significant illness and death across human populations. Above all, it is unusual for a mammal to use powered flight and hibernate in high densities like bats do with other species. They are also remarkably long-lived compared to other mammals of their size (10-20 years compared to a rat’s average of two years).

Other characteristics sometimes shared by other mammals but potentially increasing bats’ potential to act as a reservoir for these pathogens include their gregarious social behavior and mutual grooming patterns, ability to travel long distances, nocturnal activity, and broad species diversity (the second highest after rodents). This handful of unique characteristics makes bats difficult to study in controlled laboratory environments and has caused obstacles in obtaining information on why these animals are so efficient at transmitting lethal diseases to humans.

Here are a few theories scientists have on how bats transmit disease without becoming sick themselves.

Flight as fever

During the process of propelled flight over long distances, the bat’s increased metabolic body rate and body temperature could potentially result in the same protective host defenses as the immune system’s reaction to inflammation or an infectious insult3. Although we may take Tylenol or other fever-reducers to manage our body temperatures during flu or other illness, fever exists as a way to bolster our existing immune responses and decrease the severe effects of these pathogens. So, in comparing the immune system of bats to that of humans, the daily flight-associated oscillation of body temperature and associated immune responses may help explain bats’ coexistence with pathogens that they are then able to shed into the environment, causing sickness and death in species lacking this protective effect. Studies using live bats are needed to corroborate this hypothesis, which as previously alluded to is much easier said than done.

Genome contraction

Bats are also unique in that they display the evolutionary loss of specific genes, specifically those that code for proteins involved in the immune response4. By examining the genomes of different species and analyzing where they diverged in a phylogenetic tree, we may determine which genes may have been more recent ‘additions or deletions’. This is considered a form of natural selection where redundant genes are deleted – the ‘less is more’ hypothesis. A recent study showed that bats lost an entire gene family that codes for proteins sensing foreign genetic material (e.g. viruses) and regulating the effects of aging and inflammation5.

Ongoing immune signaling

Cytokines are cell signaling molecules within the immune system. One important cytokine in the immediate response of the body to any infectious insult is IFN-α. Scientists have recently discovered that bats continuously express IFN-α even in the absence of viral infection6. In other words, their immune system is constantly ramped up, knocking down any viral insult as it occurs without the bats’ health being adversely affected at all. What about the impact of stress on bats’ immune system? Events like pregnancy, extreme weather events, lack of food and resources, extreme age, or increased crowding density may impact the levels of baseline cytokine presence. Again, these are questions that may be answered utilizing live bats in the laboratory.

Each of these theories highlights unique features of the physiology and immunology of bats, perhaps hinting at a genetic "seeding out" of unnecessary genes while leaving specific genes turned on that provide them an extra first-line defense against these viruses. Consider these genetic discoveries in light of the bat’s unique lifestyle, and it is clear that much work is left to be done studying these factors and the way that different stressors may influence the immune system and metabolism. Scientists are racing to unravel the fundamental differences in immunity between bats and humans to better understand what makes them seemingly resistant to viruses like Ebola, while humans remain susceptible.

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