PULLMAN, Wash. - Why bats can harbor viruses like hantavirus and coronavirus - pathogens that are highly dangerous to humans - without becoming ill themselves has long puzzled scientists, yet the answer may be key to preventing outbreaks and fighting the diseases.
To help answer that question, a team led by Washington State University molecular virologist Michael Letko has developed two new bat-derived laboratory cell lines, providing much-needed tools for studying how bats and their immune systems respond to these viruses. The process for creating the new lines - which have been deposited with the American Type Culture Collection, a nonprofit repository for biological samples - can also importantly serve as a roadmap for creating additional lines to support future research. The research was outlined in the journal PLOS Biology.
"Bats are a reservoir for many pathogens that can infect humans and domestic animals, yet we lack effective tools to study bat viruses in the lab," said Letko, an assistant professor in WSU's College of Veterinary Medicine. "One big question is how do bats tolerate these infections? These cell lines and future research can help us uncover those mechanisms, and that could lead to new therapies for human diseases."
A cell line is a population of cells that are cultured and maintained in a laboratory for research purposes. These cells are typically derived from a single original cell and go through a process known as immortalization, which allows them to be grown and divided indefinitely under controlled conditions, making them a valuable tool for viral research.
While bat cell lines are critical for studying how these animals coexist with viruses, most labs have been limited to using the handful developed more than 50 years ago. Most viruses are species specific, and these lines come from species that often don't respond to viruses of current interest, limiting their usefulness.
The new lines were developed from kidney tissue of a Seba's short-tailed bat (Carollia perspicillata) that came from a colony maintained at WSU Vancouver by professor Christine Portfors.
The new lines support infection by a diverse group of viruses, but they will be particularly useful for studying coronaviruses and orthohantaviruses. The latter family includes sin nombre virus, which is found in the western United States and recently caused a fatal infection in Whitman County, Washington, the county in which WSU is located.
"These viruses have the potential to impact not just our own national health, but global health, because they're found all over," Letko said.
A major challenge to developing useful lines is ensuring the cells maintain their ability to mount immune responses to pathogens.
"We started off with a pile of different tissues and cells, and then we went through different immortalization routes and basically started to weed them out," Letko said. "By the end, we had a small number of cells that were immortalized in specific ways, and those were the ones that actually still retained the properties we think are going to let us study how bats actually respond to viruses."
Much research to date has relied on cell lines from humans, rodents or primates, which can't answer why bats tolerate viruses that make other species sick.
"We could study a virus like Ebola just fine in a human cell, and we can watch how it interacts with that immune system," Letko said, "but that won't help us identify the reason why bats tolerate these infections."
While some bat lines have been developed in private labs, those are not often made available to other researchers. Letko wanted to ensure their work would aid future research.
"We have a lot of really good immunologists and virologists here and elsewhere, but they just don't have access to all this specialized material," Letko said. "That creates tiers in bat research between the groups that have access and basically everybody else who had to rely on old cell lines that were collected in the 1960s."
The research, funded by the National Institutes of Health, was a collaborative effort that also included the labs of WSU researcher Stephanie Seifert and scientists from the University of Saskatchewan, University of New Mexico and Louisiana State University.
