Link to MERS Virus Underscores Bats' Puzzling Threat
Science, 341:948-949, 30 August 2013. Uncorrected OCR. You didn't hear
it from me. (The piggy AAAS wants $20 to rent access to this little
news report for a whole day.)
Last week's announcement that a fatal new
virus disease in the Middle East may have
originated in bats has focused new atten-
tion on an enduring enigma: What is it
about bats? A frightening litany of recently
arrived human diseases—including Nipah
virus, Hendra virus, severe acute respira-
tory syndrome (SARS), and now Middle
East respiratory syndrome (MERS)—came
from bats. Is there something special about
these mammals that turns them into flying
repositories of pathogens?
"That's the million dollar question," says
Jonathan Ep stein, a veterinary epidemiolo-
gist at the EcoHealth Alliance in New York
City who collected samples from bats in
Saudi Arabia for last week's paper in Emerg-
ing Infectious Diseases. Interest in the topic
is huge, says veterinary pathologist Gudrun
Wibbelt of the Leibniz Institute for Zoo and
Wildlife Research in Berlin. "It's come to the
point where you just have to add those three
words 'Are bats special?' to a paper and it will
get published," she jokes.
Some scientists do think bats are excep-
tional; they have invoked everything from
hibernation and echolocation to peculiari-
ties of bats' immune systems to explain why
the Chiroptera, as their order is known, could
pose a greater threat than others. But other
researchers don't see the need for explana-
tions beyond bats' numbers and lifestyle.
The latest finding didn't come as a big sur-
prise. Scientists already suspected that the
MERS coronavirus came from bats, as they
had found several closely related viruses in
other bat species. In the new paper, a team
led by Columbia University virologist lan
Lipkin reports finding an RNA fragment in the
feces of an Egyptian tomb bat that matched
the MERS virus exactly. They
didn't find the virus itself, and
the snippet was only 182 nucle-
otides long—but it made the
species a prime suspect as the
MERS reservoir (http://scim.
ag/MERSbats).
It's only the latest example
in a growing list. Bats have been
known to carry the rabies virus
for 60 years, but in the past
2 decades, many new diseases were traced
back to them as well. Hendra virus, which
first popped up in Australian horses and peo-
ple who worked with them in 1994, was later
found to originate in fruit bats; it has since
caused numerous outbreaks and killed at least
four humans. A surveillance program to track
it led to the discovery of another deadly patho-
gen, the Australian bat lyssavirus.
In 1998, yet another newcomer, Nipah
virus, jumped from bats to pigs in Malaysia,
and on to humans, killing more than 100 peo-
ple. The most likely predecessor to SARS,
which killed 775 people in 2002 and 2003,
was identified in horseshoe bats in China.
Investigations have also pointed to bats as the
natural reservoir for the Ebola and Marburg
viruses and for a whole list of more obscure
agents, with names like Kasokero, Duven-
hage, and Menangle.
The viruses come from many differ-
ent families. SARS and MERS are corona-
viruses; rabies, Duvenhage, and bat lys-
savirus belong to the rhabdovirus family;
whereas Nipah and Hendra are Paramyxo-
viruses. But they do have a few things in
common: They are usually RNA viruses that
replicate outside the cell's nucleus, and they
seem to have high fatality rates in humans.
The routes of infection vary. Bites can trans-
mit rabies, but more often viruses spread
when bat droppings infect an intermediate
host that lives closer to humans.
The frequent spillovers could be largely a
numbers game, Epstein says. With more than
1300 species—roughly one-fifth of all mam-
malian species—it's "not surprising" that
bats cause a sizable share of the newly emerg-
ing diseases as well, he says.
New numbers suggest that statistics can't
be the full explanation, however. Earlier this
year, Angela Luis, a biologist at Colorado
State University, Fort Collins, published an
analysis comparing bats with another huge
mammalian group, the rodents. Both har-
bor nasty viruses, are evolu-
tionarily old, display a wide
range of body sizes, and have
some hibernating species. Sift-
ing through the literature, Luis
and her colleagues identified
68 viruses in rodents that can
also cause disease in humans,
versus only 61 in bats. But
there are twice as many rodent
species, so relatively speaking,
bats appear to be a more frequent source of
emerging infections.
Even if bats unleash more zoonoses than
other animals, that doesn't mean there is any-
thing special about their physiology, Epstein
says. Bats occur on every continent except
Antarctica, and some species migrate over
hundreds of miles; species also intermingle,
for instance while roosting in caves. As a
result, they may be exposed to more viruses
than other mammals. Some species formdense populations of thousands or
millions of
individuals—a mecca for viruses.
There are other factors: Bats are long-
lived—some can live up to 40 years—which
gives them a higher chance of transmitting a
virus that they're persistently infected with.
They likely first appeared about 50 million
years ago, so viruses that evolved with them
may be using very old, conserved receptors
to gain access to cells, which might make
the jump to other mammalian species eas-
ier. Another hypothesis holds that hiberna-
tion could make animals more susceptible
to infections, but Luis found the opposite in
her analysis: Hibernating species had slightly
fewer viruses. Some scientists have even
hypothesized that generating echolocation
sounds—which come out through the mouth
or the nose—creates fountains of droplets
that help spread viruses.
Linfa Wang, who heads the "bat pack," a
research team at the Australian Animal Health
Laboratory in Geelong, thinks that bat num-
bers and behavior can't explain it all. "We
think there is something very unusual going
on in bats," he says. At conferences, propo-
nents of these two viewpoints regularly clash,
Wang says: "It's become a bit of a ritual."
He thinks that the answer lies in bats'
immune systems. Most viruses have been
isolated from healthy bats, and researchers
speculate that bats may have a remarkable
capacity to play host to viruses for long peri-
ods of time while suffering few or no symp-
toms. Earlier this year, Wang and colleagues
presented evidence for that idea in a paper
describing the first two bat genomes—one
from a small, insect-eating echolocating spe-
cies, the other from a big, fruit-eating fly-
ing fox (Science, 25 January, p. 456). Strik-
ingly, both species lacked a chunk of the
genome containing genes involved in sensing
microbial DNA and initiating an inflamma-
tion response. In addition, genes involved in
repairing DNA damage appeared to evolve
faster in bats than in other mammals.
Wang's hypothesis is that during flight,
bats have to dramatically increase their
heart rate and energy consumption. This
releases metabolites that damage DNA, he
argues, so evolution came up with special
DNA repair mechanisms. But because the
immune system uses some of the molecules
involved in DNA repair, the result was a
"robust but primitive system," that left bats
more vulnerable to infections but caused
less of the damage typically created when
a strong immune system fights a pathogen.
Better DNA correction might also explain
bats' longevity. "I think Linfa is on to some-
thing here," Lipkin says.
Other scientists are unconvinced. Wib-
belt, who has dissected hundreds of dead
bats, says that many of them may well have
died of viral infections. So little is known
about bats' immune systems that much of the
debate is pure speculation, she says. "We've
learned a few new things about bat immunity,
but at a firustratingly slow pace," adds Andrew
Dobson, an infectious diseases ecologist at
Princeton University. One problem is that bats
are not easy to study; many species are endan-
gered and lab colonies are hard to set up.
Many ecologists think that the biggest
factor in the viral spillover from bats is their
proximity to people. The tomb bats linked
to MERS, for instance, often live in old,
abandoned buildings. People could become
infected after kicking up some soil or dust
contaminated with feces and inhaling it,
Epstein says. And as humans encroach on bat
habitats, such interactions may become more
common. "The principal ecological problem
is that bat habitat is being destroyed and they
are increasingly forced to roost in fruit and
shade trees that are close to human dwell-
ings," Dobson says.
Many conservation biologists don't like
to hear about new pathogens found in bats,
because it could undermine efforts to pre-
serve them, Epstein says: "They feel every
discovery implicates bats in a bad way." But
if dwindling habitats are causing outbreaks,
that's actually an argument to take conser-
vation more seriously, he says. Bats may
turn out to carry more, and more dangerous,
viruses than other wildlife, Epstein says,
"but how these viruses manage to spill over:
That's on us." -KAI KUPFERSCHMIDT
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