The worldwide Coronavirus outbreak that has sickened more than 80,000 people and resulted in at least 2,700 deaths raises the question: “Why are bat viruses so deadly for humans?” According to a new study from the University of California, Berkeley, published this month in the journal eLife, bats’ aggressive immune response to viruses can cause bat viruses to reproduce faster, making the animals the perfect host for viruses that can then be transferred to other species, known as zoonotic viruses. As a result of this accelerated infectivity and increased virulence, zoonotic viruses can have deadly consequences when they are transferred to mammals with immune systems that are only average compared to bats’ immune systems, such as humans.
According to this new study, some bats, including those known to be the original source of human infections, have immune systems that are perpetually ready to aggressively respond to and defend against viruses. In order to demonstrate how viral infection in these bats results in a swift and effective immune response, the researchers from the University of California, Berkeley developed a simple computer model of the bats’ immune systems. The researchers showed that when bat cells quickly release interferon upon encountering a viral infection, other cells quickly wall themselves off from the infection. What this means for bats is that they can host viruses without experiencing disease. Unfortunately, it also means that these viruses are encouraged to reproduce more quickly within a host before the host’s immune system can mount a defense against the infection.
These findings explain why bat viruses can be especially deadly in humans. In fact, some of the worst viral human disease outbreaks in recent years, including Ebola, SARS, MERS and the nCoV virus, originated in bats. While the bats can tolerate the viruses, the viruses can quickly overwhelm animals that lack such a fast and highly responsive immune system, resulting in high fatality rates. “Some bats are able to mount this robust antiviral response, but also balance it with an anti-inflammation response,” says lead study author Cara Brook, a postdoctoral Miller Fellow at UC Berkeley. “Our immune system would generate widespread inflammation if attempting this same antiviral strategy. But bats appear uniquely suited to avoiding the threat of immunopathology.”
In order to determine how bats’ rapid immune response to infection affects the development of the viruses they host, the researchers studied cultured cells from two bats and one monkey, as a control. “When you have a higher immune response, you get these cells that are protected from infection, so the virus can actually ramp up its replication rate without causing damage to its host,” the researchers wrote. “But when it spills over into something like a human, we don’t have those same sorts of antiviral mechanism, and we could experience a lot of pathology.”
Many potentially deadly viruses that originate in bats are transferred through an animal intermediary. For example, SARS was transferred to humans through the Asian palm civet; Ebola via gorillas and chimpanzees; and MERS via camels. Bat viruses can be transferred to other animals via saliva, as well as aerosolization of saliva, urine and/or feces. The UC Berkeley researchers note that environmental threats to bats may “add to the threat of zoonosis.” According to Brook, who works with a bat monitoring program currently underway in Madagascar, Australia, Ghana and Bangladesh, disrupting bat habitat may stress the animals and cause them to shed even more virus in their saliva, feces and urine that can infect other animals.
“The bottom line is that bats are potentially special when it comes to hosting viruses,” says Mike Boots, a disease ecologist and UC Berkeley professor of integrative biology. “It is not random that a lot of these viruses are coming from bats. Bats are not even that closely related to us, so we would not expect them to host many human viruses. But this work demonstrates how bat immune systems could drive the virulence that overcomes this.”