Bats serve as natural hosts for numerous viruses including Ebola virus, Nipah virus, SARS, MERS and the novel coronavirus. Yet, the viruses even when present in large numbers do not cause any harmful effects. Reason: bats avoid excessive virus-induced inflammation.
Bats serve as natural hosts for numerous viruses including Ebola virus, Nipah virus, coronoviruses such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and the 2019 novel coronovirus that has infected nearly 10,000 people and killed over 200 others. Even as these viruses cause harm in humans, they rarely if at all cause any harmful effects in bats. This is the case even when the viral load is extremely high in bats.
A study carried out last year and published in the journal Nature Microbiology revealed the mechanism responsible for bats to harbour numerous viruses without themselves getting affected and also live long. Compared with terrestrial mammals, bats have longer lifespan.
The secret: No virus-induced inflammation
The reason why bats can harbour these viruses without getting affected is simply because bats can avoid excessive virus-induced inflammation, which often causes severe diseases in animals and people infected with viruses.
When pathogens infect humans and mice, the immune system gets activated and typical inflammatory response to fight the microbes is seen. While controlled inflammatory response to fight infection helps keep humans healthy, it can contribute to the damage caused by infectious diseases, and also age-related diseases when the inflammatory response becomes excessive.
Inflammatory response gets dampened
In complete contrast, the researchers found that the inflammatory response is dampened in bats immaterial of the variety of viruses that are present and the viral load. The researchers from Duke-NUS Medical School, Singapore used three different viruses — Melaka virus, MERS coronavirus and influenza A virus — and tested the responses of immune cell and other cells (peripheral blood mononuclear cells and bone-marrow derived macrophages) of bats, mice and humans to these viruses. While inflammation was high in the case of humans and mice, it was significantly reduced in bats immune cells.
“This supports an enhanced innate immune tolerance rather than an enhanced antiviral defence in bats,” they write. “This may also contribute to our understanding of the role of the inflammation in disease tolerance in bats as reservoir hosts” they say. This is in complete contrast to what is seen in mice and humans for disease-causing zoonotic viruses.
Dampening NLRP3 protein
The researchers found that significantly reduced inflammation in bats was because activation of an important protein — NLRP3 — that recognises both cellular stress and viral/bacterial infections was significantly dampened in bat immune cells.
Studying further, the researchers found that reduced activation of the NLRP3 protein was in turn due to impaired production of mRNA (transcript). Since mRNA production is impaired the NLRP3 protein production gets compromised leading to less amount of the protein being produced. But this was not the case with mice and humans — there was no impairment to mRNA production so the NLRP3 protein was unaffected.
The NLRP3 protein is found as four variants in bats. The researchers found that the function of all the four variants in bats was dampened compared with human NLRP3. To test if their finding on NLRP3 hold true in evolutionally distant bats, the researchers studied two very distinct species of bats — Pteropus alecto, which is a large fruit bat known as the Black Flying Fox, and Myotis davadii, a tiny vesper bat from China. The variations have been found to be genetically conserved through evolution.
Further analysis comparing 10 bat and 17 non-bat mammalian NLRP3 gene sequences confirmed that these adaptations appear to be bat-specific.