Viruses that are related to SARS and that are found in some species of bats could become a source of future human outbreaks, according to a new study released Monday. And it appears that there are fewer barriers to that spillover than scientists initially thought.
Researchers at the University of North Carolina at Chapel Hill said a virus in the same family as SARS — severe acute respiratory syndrome — appears to be able to infect human respiratory tract cells. The finding came as a surprise because the team thought the virus would have had to go through a process known as adaptation — meaning it would have had to acquire the ability to infect human cells by first learning how to infect the cells of another mammal.
It’s believed that is how SARS went from being a bat virus to a major international outbreak that infected 8,400 people in 2003, killing at least 916 of them. In the case of SARS, the virus was probably passed from bats to palm civets and from palm civets to people.
The new study was published in the journal Nature Medicine.
The UNC scientists wanted to see if cousin viruses — coronaviruses that are carried by Chinese horseshoe bats — also posed a threat to people. They used one, SHC014, as a representative of the group.
They inserted a key part of the virus, its spike protein, into a SARS virus and then ran experiments to see if the hybrid virus could infect human respiratory tract cells (in a dish) and mice that were vulnerable to the SARS virus.
“I think the existence of viruses that can jump directly is the important part, that was unanticipated,” lead author Vineet Menachery, who researches viral immunology, told STAT in an interview.
“Based on what was known in the literature, we would have expected that viruses coming out of bats would have needed that one-in-million mutation.”
Another coronavirus expert, Dr. Stanley Perlman at the University of Iowa, suggested the paper was a useful investigation. But he noted the hybrid virus was attenuated — weakened — and said the virus would probably need to adapt more in people before it could spread widely.
SARS wasn’t a highly transmissible virus. Many patients didn’t infect anyone else during the 2003 outbreak. Once hospitals learned how to recognize the disease and put stringent infection control measures in place — isolating patients and requiring staff treating them to wear the right protective equipment — the outbreak was contained.
The SHC014 virus is part of a cluster of related coronaviruses, explained senior author Ralph Baric, a professor of epidemiology at UNC. Some are quite similar to the SARS virus while others are more distant relatives, varying in terms of their genetic structures by between 5 percent and 60 percent. SHC014 was about 12 percent different from SARS.
A coronavirus expert, Baric said if the viruses were too distantly related to SARS — more than 25 percent different — they would not be able to make a hybrid that would infect human cells. “Not all SARS-like coronaviruses have the inherent potential to replicate in mammalian cells and replicate in human cells.”
And being able to do something in the artificial confines of a laboratory does not guarantee it will happen in nature. For a bat virus to start infecting people, the bat would have to come into contact with people in a way that would allow transmission. Even if a single person became infected, the virus would have to work efficiently in human cells, producing lots of copies of itself that could be coughed or sneezed out toward the airways of other people.
“There are a lot of steps down this road,” Menachery said. “SHC014 has taken a step ahead. But there’s still a lot of other factors that are involved.”
He and his co-authors noted they had to stop some of their work because of US government policies. The US has a moratorium on so-called gain-of-function research, which includes some research that enhances the ability of a pathogen such as a virus to infect people or spread among them.
The authors expressed concern their findings might prompt further constraints on their work — something Dutch virologist Ron Fouchier hoped the team could avoid. Fouchier’s publication of a paper exploring what it would take to make H5N1 bird flu viruses more transmissible was one of the triggers for the gain-of-function research review.
Figuring out the potential these viruses have to infect people is important, said Fouchier, who works at Erasmus Medical Center in Rotterdam, especially in light of ongoing outbreaks involving the coronavirus known as MERS, or Middle East respiratory syndrome. Scientific shorthand for coronavirus is CoV.
“The MERS-CoV continues to cause problems, and we need to deal with that virus with whatever technology and lab work we have available, including gain-of-function research if needed,” Fouchier said in an email.