Scientific American reports:

Before SARS, the world had only an inkling of coronaviruses—so named because their spiky surface resembles a crown when seen under a microscope, says Linfa Wang, who directs the emerging infectious diseases program at Singapore’s Duke-NUS Medical School. Coronaviruses were mostly known for causing common colds. “The SARS outbreak [in 2003] was a game changer,” Wang says. It was the first emergence of a deadly coronavirus with pandemic potential. The incident helped to jump-start a global search for animal viruses that could find their way into humans. Shi [Zhengli, a virologist who is often called China’s “bat woman” by her colleagues because of her virus-hunting expeditions in bat caves over the past 16 years] was an early recruit of that effort, and both [Peter] Daszak and Wang have been her long-term collaborators.

With the SARS virus, just how the civets got it remained a mystery. Two previous incidents were telling: Australia’s 1994 Hendra virus infections, in which the contagion jumped from horses to humans, and Malaysia’s 1998 Nipah virus outbreak, in which it moved from pigs to people. Wang found that both diseases were caused by pathogens that originated in fruit-eating bats. Horses and pigs were merely the intermediate hosts. Bats in the Guangdong market also contained traces of the SARS virus, but many scientists dismissed this as contamination. Wang, however, thought bats might be the source.

In those first virus-hunting months in 2004, whenever Shi’s team located a bat cave, it would put a net at the opening before dusk and then wait for the nocturnal creatures to venture out to feed for the night. Once the bats were trapped, the researchers took blood and saliva samples, as well as fecal swabs, often working into the small hours. After catching up on some sleep, they would return to the cave in the morning to collect urine and fecal pellets.

But sample after sample turned up no trace of genetic material from coronaviruses. It was a heavy blow. “Eight months of hard work seemed to have gone down the drain,” Shi says. “We thought maybe bats had nothing to do with SARS.” The scientists were about to give up when a research group in a neighboring lab handed them a diagnostic kit for testing antibodies produced by people with SARS.

There was no guarantee that the test would work for bat antibodies, but Shi gave it a go anyway. “What did we have to lose?” she says. The results exceeded her expectations. Samples from three horseshoe bat species contained antibodies to the SARS virus. “It was a turning point for the project,” Shi says. The researchers learned that the presence of the coronavirus in bats was ephemeral and seasonal—but an antibody reaction could last from weeks to years. The diagnostic kit, therefore, offered a valuable pointer as to how to hunt down viral genomic sequences.

Shi’s team used the antibody test to narrow down the list of locations and bat species to pursue in the quest for genomic clues. After roaming mountainous terrain in most of China’s dozens of provinces, the researchers turned their attention to one spot: Shitou Cave, on the outskirts of Kunming, the capital of Yunnan, where they conducted intense sampling during different seasons over five consecutive years.

The efforts paid off. The pathogen hunters discovered hundreds of bat-borne coronaviruses with incredible genetic diversity. “The majority of them are harmless,” Shi says. But dozens belong to the same group as SARS. They can infect human lung cells in a petri dish and cause SARS-like diseases in mice.

In Shitou Cave—where painstaking scrutiny has yielded a natural genetic library of bat-borne viruses—the team discovered a coronavirus strain that came from horseshoe bats with a genomic sequence nearly 97 percent identical to the one found in civets in Guangdong. The finding concluded a decade-long search for the natural reservoir of the SARS coronavirus.

In many bat dwellings Shi has sampled, including Shitou Cave, “constant mixing of different viruses creates a great opportunity for dangerous new pathogens to emerge,” says Ralph Baric, a virologist at the University of North Carolina at Chapel Hill. In the vicinity of such viral melting pots, Shi says, “you don’t need to be a wildlife trader to be infected.”

Near Shitou Cave, for example, many villages sprawl among the lush hillsides in a region known for its roses, oranges, walnuts and hawthorn berries. In October 2015 Shi’s team collected blood samples from more than 200 residents in four of those villages. It found that six people, or nearly 3 percent, carried antibodies against SARS-like coronaviruses from bats—even though none of them had handled wildlife or reported SARS-like or other pneumonialike symptoms. Only one had traveled outside of Yunnan prior to the sampling, and all said they had seen bats flying in their village. [Continue reading…]