In the summer of 2020, half a year into the coronavirus
pandemic, scientists traveled into the forests of northern Laos to catch bats
that might harbor close cousins of the pathogen.
اضافة اعلان
In the dead of night, they used mist nets and canvas traps to
snag the animals as they emerged from nearby caves, gathered samples of saliva,
urine and feces, then released them back into the darkness.
The fecal samples turned out to contain coronaviruses, which the
scientists studied in high-security biosafety labs, known as BSL-3, using
specialized protective gear and air filters.
Three of the Laos coronaviruses were unusual: They carried a
molecular hook on their surface that was very similar to the hook on the virus
that causes COVID-19, called SARS-CoV-2. Like SARS-CoV-2, their hook allowed
them to latch onto human cells.
“It is even better than early strains of SARS-CoV-2,” said Marc
Eloit, a virus expert at the Pasteur Institute in Paris who led the study,
referring to how well the hook on the Laos coronaviruses binds to human cells.
The study was posted online last month and has not yet been published in a
scientific journal.
Virus experts are buzzing about the discovery. Some suspect that
these SARS-CoV-2-like viruses may already be infecting people from time to
time, causing only mild and limited outbreaks. But under the right
circumstances, the pathogens could give rise to a COVID-19-like pandemic, they
say.
The findings also have significant implications for the charged
debate over COVID’s origins, experts say. Some people have speculated that
SARS-CoV-2’s impressive ability to infect human cells could not have evolved
through a natural spillover from an animal. But the new findings seem to
suggest otherwise.
“That really puts to bed any notion that this virus had to have
been concocted or somehow manipulated in a lab to be so good at infecting
humans,” said Michael Worobey, a University of Arizona virus expert who was not
involved in the work.
These bat viruses, along with more than a dozen others
discovered in recent months in Laos, Cambodia, China and Thailand, may also
help researchers better anticipate future pandemics. The viruses’ family trees
offer hints about where potentially dangerous strains are lurking and which
animals scientists should look at to find them.
Last week, the U.S. government announced a $125 million project
to identify thousands of wild viruses in Asia, Latin America and Africa to
determine their risk of spillover. Eloit predicted that there were many more
relatives of SARS-CoV-2 left to find.
“I am a fly fisherman,” he said. “When I am unable to catch a
trout, that doesn’t mean there are no trout in the river.”
When SARS-CoV-2 first came to light, its closest known relative
was a bat coronavirus that Chinese researchers found in 2016 in a mine in
southern China’s Yunnan province. RaTG13, as it is known, shares 96 percent of
its genome with SARS-CoV-2. Based on the mutations carried by each virus,
scientists have estimated that RaTG13 and SARS-CoV-2 share a common ancestor
that infected bats about 40 years ago.
Both viruses infect cells by using a molecular hook, called the
“receptor-binding domain,” to latch onto their surface. RaTG13’s hook, adapted
for attaching to bat cells, can only cling weakly to human cells. SARS-CoV-2’s
hook, by contrast, can clasp cells in the human airway, the first step toward a
potentially lethal case of COVID-19.
To find other close relatives of SARS-CoV-2, wildlife virus
experts checked their freezers full of old samples from across the world. They
identified several similar coronaviruses from southern China, Cambodia and
Thailand. Most came from bats, while a few came from scaly mammals known as
pangolins. None was a closer relative than RaTG13.
Eloit and his colleagues instead set out to find new
coronaviruses.
They traveled to northern Laos, about 150 miles from the mine
where Chinese researchers had found RaTG13. Over six months they caught 645
bats belonging to 45 different species. The bats harbored two dozen kinds of
coronaviruses, three of which were strikingly similar to SARS-CoV-2 —
especially in the receptor-binding domain.
In RaTG13, 11 of the 17 key building blocks of the domain are
identical to those of SARS-CoV-2. But in the three viruses from Laos, as many
as 16 were identical — the closest match to date.
Eloit speculated that one or more of the coronaviruses might be
able to infect humans and cause mild disease. In a separate study, he and
colleagues took blood samples from people in Laos who collect bat guano for a
living. Although the Laotians did not show signs of having been infected with
SARS-CoV-2, they carried immune markers, called antibodies, that appeared to be
caused by a similar virus.
Linfa Wang, a molecular virus expert at the Duke-NUS Medical
School in Singapore who was not involved in the study, agreed that such an
infection was possible, since the newly discovered viruses can attach tightly
to a protein on human cells called ACE2.
“If the receptor-binding domain is ready to use ACE2, these guys
are dangerous,” Wang said.
Paradoxically, some other genes in the three Laotian viruses are
more distantly related to SARS-CoV-2 than other bat viruses. The cause of this
genetic patchwork is the complex evolution of coronaviruses.
If a bat infected with one coronavirus catches a second one, the
two different viruses may end up in a single cell at once. As that cell begins
to replicate each of those viruses, their genes get shuffled together,
producing new virus hybrids.
In the Laotian coronaviruses, this gene shuffling has given them
a receptor-binding domain that is very similar to that of SARS-CoV-2. The
original genetic swap took place about a decade ago, according to a preliminary
analysis by Spyros Lytras, a graduate student at the University of Glasgow in
Scotland.
Lytras and his colleagues are now comparing SARS-CoV-2 not just
to the new viruses from Laos, but to other close relatives that have been found
in recent months. They are finding even more evidence of gene shuffling. This
process — known as recombination — may be reshaping the viruses from year to
year.
“It’s becoming more and more obvious how important recombination
is,” Lytras said.
He and his colleagues are now drawing the messy evolutionary
trees of SARS-CoV-2-like viruses based on these new insights. Finding more
viruses could help clear up the picture. But scientists are divided as to where
to look for them.
Eloit believes the best bet is a zone of Southeast Asia that
includes the site where his colleagues found their coronaviruses, as well as
the nearby mine in Yunnan where RaTG13 was found.
“I think the main landscape corresponds to north Vietnam, north
Laos and south China,” Eloit said.
The US government’s new virus-hunting project, called DEEP VZN,
may turn up one or more SARS-CoV-2-like viruses in that region. A spokesperson
for USAID, the agency funding the effort, named Vietnam as one of the countries
where researchers will be searching and said that new coronaviruses are one of
their top priorities.
Colin Carlson, a biologist at Georgetown University, suspects
that a virus capable of producing a COVID-like outbreak might be lurking even
farther away. Bats as far east as Indonesia and as far west as India, he noted,
share many biological features with the animals known to carry SARS-CoV-2-like
viruses.
“This is not just a Southeast Asia problem,” Carlson said.
“These viruses are diverse, and they are more cosmopolitan than we have
thought.”
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