Coronavirus outbreak raises question: Why are bat viruses so deadly? It’s no coincidence that some of the worst viral disease outbreaks in recent years — SARS, MERS, Ebola, Marburg and likely the newly arrived COVID-19 — originated in bats.
A new University of California, Berkeley, study, supported in part by the U.S. National Science Foundation, finds that bats’ fierce immune response to viruses could drive viruses to replicate faster, so that when they jump to mammals with average immune systems, such as humans, the viruses wreak deadly havoc.
Some bats — including those known to be the original source of human infections — have been shown to host immune systems that are perpetually primed to mount defenses against viruses. Viral infection in these bats leads to a swift response that walls the virus out of cells. While this may protect the bats from getting infected with high viral loads, it encourages these viruses to reproduce more quickly within a host before a defense can be mounted.
This makes bats a unique reservoir of rapidly reproducing and highly transmissible viruses. While the bats can tolerate viruses like these, when these bat viruses then move into animals that lack a fast-response immune system, the viruses quickly overwhelm their new hosts, leading to high fatality rates.
“The bottom line is that bats are potentially special when it comes to hosting viruses,” said 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.”
The new study by Brook, Boots and their colleagues was published this month in the journal eLife.
Brook was curious how bats’ rapid immune response affects the evolution of the viruses they host, so she conducted experiments on cultured cells from two bats and, as a control, one monkey. One bat, the Egyptian fruit bat, a natural host of 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, a reservoir of Hendra virus, which is primed to fight virus infections with interferon-alpha RNA that is transcribed and ready to turn into protein. The African green monkey (Vero) cell line does not produce interferon at all. When challenged by viruses mimicking Ebola and Marburg, the different responses of these cell lines were striking. While the green monkey cell line was rapidly overwhelmed and killed by the viruses, a subset of the rousette bat cells successfully walled themselves off from viral infection, thanks to interferon early warning.
In the Australian black flying fox cells, the immune response was even more successful, with the viral infection slowed substantially over that in the rousette cell line. In addition, these bat interferon responses seemed to allow the infections to last longer.
“Think of viruses on a cell monolayer like a fire burning through a forest. Some of the communities — cells — have emergency blankets, and the fire washes through without harming them, but at the end of the day you still have smoldering coals in the system — there are still some viral cells,” Brook said. The surviving communities of cells can reproduce, providing new targets for the the virus and setting up a smoldering infection that persists across the bat’s lifespan.
Brook and Boots created a simple model of the bats’ immune systems to recreate their experiments in a computer.
The researchers noted that many of the bat viruses jump to humans through an animal intermediary. SARS got to humans through the Asian palm civet; MERS via camels; Ebola via gorillas and chimpanzees; Nipah via pigs; Hendra via horses and Marburg through African green monkeys. Nonetheless, these viruses still remain extremely virulent and deadly upon making the final jump into humans.
Brook and Boots are designing a more formal model of disease evolution within bats in order to better understand virus spillover into other animals and humans.
Other co-authors of the eLife paper are Kartik Chandran and Melinda Ng of Albert Einstein College of Medicine in New York City; Andrew Dobson, Andrea Graham, Bryan Grenfell and Anieke van Leeuwen of Princeton University in New Jersey; Christian Drosten and Marcel Müller of Humboldt University in Berlin, Germany; and Lin-Fa Wang of Duke University-National University of Singapore Medical School.
The work was funded by a National Science Foundation fellowship, the Miller Institute for Basic Research at UC Berkeley and a grant from the National Institutes of Health (R01 AI134824).
