The outbreak of the corona virus raises a question: why are bat viruses so deadly?

The strong immune systems of bats make viruses more resistant, which makes them more deadly in humans and how does this relate to the enormous lifespan of bats?

A study conducted on cultured bat cells shows that their strong immune responses, which are constantly required to respond to viruses, can make viruses more resistant and, as a result, to a rapid rate of spread. The researchers developed a computer simulation of the bats' immune system and showed that when bat cells rapidly release interferon after infection, the viruses move away from the cells. This causes longips to multiply faster. The mutated viruses, with their increased infection rates wreak havoc when these viruses infect animals with complex immune systems, such as humans.
It is no coincidence that some of the worst viral disease outbreaks in recent years - SARS, MERS, Ebola, Marburg and the new nCoV virus that recently arrived in 2019 - seem to originate from bats.

Research at the University of California, Berkeley, reveals that bats' strong immune response to viruses may result in the emergence of viruses that replicate themselves faster, and so when they jump into mammals with average immune systems, such as humans, they cause potentially fatal damage.

Some bats – including those known to be the source of human infections – have been shown to be good hosts for viruses. Their immune systems are on constant alert to protect against viruses and this leads to a rapid response that removes the virus from the cells. While this may protect the bats from becoming infected with viruses and often developing disease, it encourages these viruses to multiply more rapidly within the host before an immune response can be developed against them.

This feature makes bats a unique pool of viruses that multiply quickly and have a high infection rate. While bats can tolerate such viruses, when these bat viruses are transferred to animals that lack a fast-reacting immune system, the viruses attack their new hosts and multiply at high rates.

Cara Brock, Miller Postdoctoral Fellow at UC Berkeley and first author of the study, said that "several bat species are able to amplify this strong antiviral response, but also balance it with an anti-inflammatory response. Our immune system will create widespread inflammation if we try the same antiviral strategy. But bats seem uniquely suited to avoid the threat of immunopathology."

The researchers point out that disrupting the bats' habitat puts them under stress and causes them to excrete even more viruses in their saliva, urine and feces that can infect other animals.
"Increased environmental threats to bats may add to the threat of the spread of dangerous viruses," said Brooke, who works in a DARPA (US Defense Advanced Research Agency) funded bat monitoring program currently taking place in Madagascar, Bangladesh, Ghana and Australia. The project examines the relationship between the loss of bat habitat and the spread of bat viruses to other animals and humans.
Mike Botts, a disease ecologist and professor of integrative biology at Berkeley says: "It's no coincidence that a lot of these viruses come from bats. Bats aren't even closely related to us so we wouldn't expect them to host many human viruses. But this study illustrates how bat immune systems can cause this result."
The new study by Brooke, Boots and their colleagues was published this month in the journal eLife.

Vigorous flying leads to a longer life span - and perhaps to tolerance to viruses

As the only flying mammal, bats increase their metabolic rate while flying to a level that doubles that of rodents of similar size when running.

In general, vigorous physical activity and high metabolic rates cause greater tissue damage due to the accumulation of harmful molecules produced during metabolism, mainly free radicals. But to enable flight, bats seem to have developed physiological mechanisms to effectively neutralize these destructive molecules.

A side benefit of effectively neutralizing harmful molecules that are created due to inflammation for any reason, may explain the uniquely long lifespan of bats. Smaller animals have faster metabolic rates and heart rates and generally have shorter lifespans than larger animals with slower heartbeats and slower metabolisms, presumably because a higher metabolism results in the production of more destructive free radicals. But bats are unique in that they have a much longer life span than other mammals of the same size: some bats can live 40 years, while a rodent of the same size may live two years.

A quick cessation of the infection may have another advantage: infection associated with an antiviral immune response. One key trick in the immune systems of many bats is the secretion of a signaling molecule called interferon-alpha into the hair, which tells other cells to "man the battle stations" before a virus invades.

Brooke was curious to know how the rapid immune response of bats affects the development of the viruses they host, so she performed experiments on cell cultures from two bats and, as a control, one monkey. One bat, the Egyptian fruit bat (Rousettus aegyptiacus), a natural host of Marburg virus, requires a direct viral attack before it increases production of 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), which serves as a reservoir of Hendra virus, designed to fight virus infections with interferon-alpha RNA that is transcribed and ready to be turned into protein. The cell culture of the African green monkey (Vero) does not produce any interferon at all.

When she infected the cell cultures with viruses that mimic Ebola and Marburg diseases, the different responses of these cell cultures were amazing. While the cell cultures of the green monkeys were quickly overwhelmed and destroyed by the viruses, a subset of the fruit bat cells were able to successfully protect themselves from viral infection, thanks to the interferon's early warning.
In the Australian black flying fox cells, the immune response was even more successful, with viral infection significantly slower than in the fruit bat cell culture. Also, these interferon responses in bats appear to allow infections to last longer.

"It is important for viruses that attack cells like for a fire that prevails in the forest. Some of the communities - the cells - have emergency blankets, and the fire passes without harming them, but at the end of the day there are still stinking coals in the area. And accordingly there are still some viral cells," said Brooke. The surviving cell communities can multiply, providing new targets for the virus and leaving a foul-smelling infection that persists throughout the bat's life.

Brock and Boots created a simple model of the bats' immune systems to reproduce their experiments on the computer.
"This suggests that using a strong interferon system will help these viruses persist within the host," Brooke said. "When you have a higher immune response, the cells are protected from infection, and so the virus can actually increase its replication rate without harming its host. But when it comes to something like a human being, we don't have the same kinds of antiviral mechanisms, so we experience pathological damage."

The researchers noted that many of the bat viruses jump to humans through intermediary animals. SARS reached humans through the Asian palm kernel; MERS through camels; Ebola through gorillas and chimpanzees; sifted through pigs; Hendra through horses and Marburg through African green monkeys. However, these viruses still remain and are extremely deadly when making the final jump to humans.

Brock and Botts are working on a better model of disease development in bats to better understand the spread of the virus to other animals and humans.
"It is important to understand the mechanisms of infection and the protective capacity of the immune systems to be able to predict emergence and spread and transmission," said Brooke.

for the scientific article

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