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    How China’s Bat Caves Hold the Secret to Preventing Epidemics

    Researchers are racing to understand why the winged creatures are teeming with fatal viruses, but don’t get sick themselves.

    HUBEI, Central China — On a balmy spring evening, Luo Dongsheng and his team hike through lush, mountainous countryside to the mouth of a vast cave. Beneath their feet lie layers of bat dung; thousands of winged black dots crowd the cavern walls. At the entrance, the team suspend a net between four strong bamboo poles and settle down to wait.

    A few minutes later, several roundleaf bats fly into the net. Carefully, Luo loosens one of the 10-centimeter specimens from the netting, takes a cotton swab, and quickly wipes the bat’s mouth and anus. The swab then goes into a plastic sample tube. The team follows Luo’s lead for three hours, eventually catching more than 40 bats.

    A tall Ph.D. student with an easy smile, 26-year-old Luo is part of a team of researchers from the Wuhan Institute of Virology (WIV). Their one-day expedition to Taiyi Cave — a cavern 2,200 meters deep, located 100 kilometers south of Hubei’s provincial capital, Wuhan — is less about the bats themselves than the viruses they carry.

    Bats are natural reservoirs for viruses, many of which can prove fatal to humans and other mammals. In the 1930s, Trinidadian scientists showed that blood-lapping vampire bats can transmit rabies to other species. Since then, scientists in Europe, North America, and Australia have identified more than 60 bat-borne viruses that can infect humans, including Ebola, which killed more than 11,000 people in West Africa between 2013 and 2016.

    Viruses invade living cells, where they replicate and sometimes sicken the host organism. Yet scientists remain mystified as to how bats can host large numbers of deadly viruses seemingly without becoming infected themselves, as well as how viruses jump from bats to other species. Answers to these questions have the potential to help eliminate epidemics in human populations.

    The WIV was founded in 1956 and its Emerging Viruses Group, led by Luo’s supervisor Shi Zhengli, has been studying bat-borne viruses since 2004. Luo and his fellow researchers’ Hubei expedition is but one leg of a regular sampling tour that takes them from the Tibetan highlands to the southern coast. Not all expeditions are as relaxed as the one at Taiyi Cave, Luo says. Last year, he braved steep cliffs and treacherous thorn bushes to reach previously unstudied caves in Guangdong.

    “Samples like these are of great value,” Luo later says from the comparative comfort of the WIV’s laboratories, where freezers store thousands of virus samples at minus 80 degrees Celsius. “When there is a new outbreak [of disease], we can search the database, trace where the virus originated, and find out why it occurred in that location.”

    Last year, when 24,000 pigs in Guangdong province died of a mysterious illness, the WIV’s freezers held the key to the disease’s origin: a coronavirus carried by native populations of horseshoe bats that is similar to SARS, the virus that killed more than 300 people on the Chinese mainland in 2003.

    When Luo and the team sampled bats near the site of the epidemic, the results were inconclusive. Only when they raided the freezers for samples collected from the same area several years before did they finally find a genetic match, naming it the swine acute diarrhea syndrome (SADS) coronavirus. The team published their findings in the journal Nature in April this year.

    “Without abundant samples, we could not have drawn this conclusion, even though we knew the virus was bat-related,” says Zhou Peng, the article’s lead author and another researcher at the Emerging Viruses Group.

    In the last few years, the international scientific community has reached a consensus to constantly monitor viruses and other emerging pathogens. There are more than 100 known virus families, 25 of which contain species transmissible to human beings. But even within those 25 families, an estimated 1.67 million species are still to be discovered. PREDICT, an international project run by the U.S.-based nonprofit EcoHealth Alliance that also sponsors some of the WIV’s work, aims to detect newly discovered viruses and map epidemic hot spots across more than 30 countries. The Global Virome Project has an even more ambitious plan: to identify every virus species in the world.

    Zhou also studies the pathogenicity of emerging viruses — the rates at which they infect humans and other animals. “We test the virus on [isolated] human cells or genetically modified mice to see if they become infected,” he says.

    Infection means that the virus could be potentially dangerous to humans and would require close monitoring. Researchers are still unsure whether or not the SADS virus can be transmitted to humans.

    Zhou began studying bat immune systems about nine years ago, when he was a Ph.D. candidate at the Australian Animal Health Laboratory — one of Australia’s top biosafety research institutes. He hoped to identify why bats can coexist with harmful viruses without getting sick. A 2016 study co-authored by Zhou found that bats maintain relatively high levels of interferon, a so-called signaling protein released by cells in the presence of viruses and other pathogens. Even in the absence of viral infections, bats release more interferon than other mammals. “It means the guards are always there,” Zhou says.

    Another of Zhou’s recent studies proposed that bats are remarkably resilient to infections because they produce limited inflammatory responses to viral diseases. “Human beings usually overreact with inflammation when infected by viruses,” Zhou says. “The ultimate target of our research is to find out the ways that bats fight against viruses and use these methods on people.”

    The WIV’s ultimate goal is to predict and prevent epidemics. Its research on bat-borne viruses began in 2004, a year after the initial SARS outbreak. At the time, China lacked an extensive disease control system; although the initial SARS outbreak took place in Guangdong, it soon spread to several northern cities and eventually into several North American and European countries. Last year, the WIV proved that the deadly SARS virus originated from bats in southwestern China’s Yunnan province, not from civet cats as previously thought.

    At present, the most effective protection against infectious diseases is vaccination. But developing vaccines is time-consuming and generally targets a single form of a virus. At the same time, viruses often mutate into new, often-untreatable forms. “It’s like a race against time,” Zhou says.

    Since the early 2000s, scientists around the world have embraced the concept of One Health, a combination of disciplines that more generally connects human health with that of animals and the environment. The WIV is orienting its research in this direction.

    “In the past, we focused on human society and responded passively to every virus epidemic,” says Zhou, who is part of a working group at the WIV that sequences coronaviruses and feeds the data into a genetic database. “Now we’re moving the defensive line forward a little bit and eliminating [diseases] when they emerge.”

    But some viruses are hard to trace, even with cutting-edge technology. Luo, Zhou’s colleague, has been scanning bat samples for lyssaviruses, a genus that causes rabies. Experts have assumed that lyssaviruses exist in China — with rabies cases sometimes making the news — but despite testing more than 3,000 bat samples in the past year, Luo hasn’t yet found any.

    By 8:30 p.m., Luo’s team has collected a full rack of swabs and bagged a dozen live bats for further testing back at the lab. Luo hopes that this time, the results will come out differently. His colleague points out a firefly bobbing up and down in the pitch-black cave. “It might be a good omen,” Luo says with a smile.

    Editor: Matthew Walsh.

    (Header image: A researcher holds a horseshoe bat at Taiyi Cave in Xianning, Hubei province, May 3, 2018. Wang Yiwei/Sixth Tone)