Sat. Feb 29th, 2020

Why are bat viruses, such as coronaviruses, so aggressive to humans?

A study by the University of California at Berkeley (United States) has concluded that the fierce immune response of bats to viruses could cause them to replicate more quickly, so that when they jump to mammals with normal immune systems, such as humans , viruses wreak havoc with more damage.

In his work, published in the magazine ‘ELife’, the researchers explain that “it is no coincidence” that some of the worst outbreaks of viral diseases in recent years, such as SARS, MERS, Ebola and the newcomer new coronavirus originated in bats.

It has been shown that some bats, including those known to be the original source of human infections, harbor immune systems that are perpetually prepared to mount defenses against viruses. The viral infection in these bats leads to a rapid response that separates the virus from the cells.

Although this can protect bats from being infected with high viral loads, it encourages these viruses to reproduce more quickly within the host before a defense can be articulated.

This makes bats a unique reservoir of rapidly reproducible and highly transmissible viruses. While bats can tolerate viruses like these, when these viruses are transmitted to animals that lack a rapid response immune system, Viruses greatly affect their new hosts, which leads to high mortality rates.

“Some bats are able to mount this robust antiviral response, but also to balance it with an anti-inflammatory response. Our immune system would generate widespread inflammation if this same antiviral strategy is attempted. But bats seem to be the most suitable to avoid the threat of immunopathology, ”explains one of the leaders of this research, Cara Brook.

Its habitat is also important

The researchers point out that Bats’ habitat disturbance seems to stress these animals, and causes them to shed even more viruses in their saliva, urine and feces. They can infect other animals. “The increase in environmental threats to bats can add to the threat of zoonosis,” says Brook.

This researcher works in a bat surveillance program funded by the United States Defense Advanced Research Projects Agency (DARPA) that is being carried out in Madagascar, Bangladesh, Ghana and Australia.

The initiative, called ‘Bat One Health’, explores the link between the loss of bat habitat and the spread of bat viruses to other animals and humans. “The bottom line is that bats are potentially special when it comes to harboring viruses. It is no accident that many of these viruses come from bats. Bats are not even so closely related to us, so we would not expect them to harbor many human viruses. But this work demonstrates how the immune system of bats could boost their virulence, ”summarizes another author, Mike Boots.

The importance of your flight

As the only flying mammal, bats raise their metabolic rates in flight to a level that doubles that reached by rodents of similar size when they run.

As usual, vigorous physical activity and high metabolic rates lead to greater tissue damage due to the accumulation of reactive molecules, mainly free radicals. But to allow flight, bats seem to have developed physiological mechanisms to effectively clean up these destructive molecules.

The researchers argue that this has the secondary benefit of efficiently cleaning up harmful molecules produced by inflammation of any cause, which may explain the long life of bats.

Smaller animals with a faster heart rate and metabolism tend to have a shorter life than larger animals with a slower heart rate and metabolism, presumably because a high metabolism produces more destructive free radicals.

But bats are unique in having a much longer life than other mammals of the same size: some can live 40 years, while a rodent of the same size can live two. This rapid reduction in inflammation may also have another advantage: reduce inflammation related to the antiviral immune response.

A key trick of the bat’s immune system is the release of a signaling molecule called interferon-alpha, which tells other cells to “prepare” before a virus invades.

Brook was curious to know how the rapid immune response of bats affects the evolution of the viruses they harbor, so he carried out experiments with cultured cells of two bats and, as a control, of a monkey.

A bat, the Egyptian fruit bat (‘Rousettus aegyptiacus’), a natural host of the Marburg virus, requires a direct viral attack before transcribing its interferon-alpha gene to flood the body with interferon.

This technique is slightly slower than that of the Australian black flying fox (‘Pteropus alecto’), a reservoir of the Hendra virus, which is prepared to fight viral infections with interferon-alpha RNA that is transcribed and is ready to become protein. The African green monkey (‘Chlorocebus sabaeus’) cell line does not produce interferon at all.

The interferon

Being challenged by viruses that mimic Ebola and Marburg, the different responses of these cell lines were surprising to scientists. While the green monkey cell line was quickly overwhelmed and eliminated by viruses, a subset of the fruit’s Egyptian bat cells was successfully isolated from viral infection, thanks to the early warning of interferon.

In Australian black flying fox cells, the immune response was even more satisfactory, since the viral infection was substantially reduced more than in the Egyptian fruit bat cell line. In addition, these bat interferon responses seemed to allow infections to last longer.

“This suggests that having a really robust interferon system would help these viruses persist inside the host. When you have a higher immune response, you get these cells that are protected from infection, so the virus can really increase its replication rate without causing damage to its host.

But when it comes to something like a human, we don’t have that same type of antiviral mechanism, and we could experience many pathologies, ”says Brook. Scientists remember that many of the bat viruses jump to humans through an animal intermediary.

SARS reached humans through the common palm civet; the MERS for camels; Ebola for gorillas and chimpanzees; the Nipah through the pigs; Hendra for the horses and the Marburg through the African green monkeys.

However, these viruses remain extremely virulent and deadly by making the final leap to humans. Now, Brook and Boots are designing a more formal model of the disease’s evolution within bats to better understand the spread of the virus in other animals and humans. “It is really important to understand the path of an infection in order to predict its appearance, spread and transmission,” the researchers conclude. Ep


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