Many questions remain, weeks into the coronavirus outbreak. Given the early and close linkage of the outbreak to a Huanan seafood market in Wuhan, China—which also sold animals such as birds and rabbits—the identification of the host of the virus and the route it took into humans has emerged as one of the biggest, earliest questions. Thanks to several Chinese research teams who performed genomic analysis on viruses isolated from patients, the puzzle pieces are coming together. The novel coronavirus, nCoV-2019, has been linked to bats.
The earliest report, published on January 23, came from a team at the Wuhan Institute of Virology, Chinese Academy of Sciences in Wuhan, China. Their study, published on the bioRxiv preprint server, is titled “Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin.”
Another report, published in The Lancet on January 30, “Genomic characterization and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding,” came from a group in the Chinese Center for Disease Control and Prevention, Beijing, China.
The Wuhan team performed genomic sequencing on samples from five patients at the early stage of the outbreak. Obtaining full-length genome sequences, they found that the five strains are almost identical to each other and that nCoV-2019 is 96% identical to a bat coronavirus. In addition, they found 79.5% identity to severe acute respiratory syndrome coronavirus (SARS-CoV) and confirmed that nCoV-2019 uses the same cell entry receptor, ACE2, as SARS-CoV.
The Lancet paper analyzed 10 genome sequences from nine patients, eight of whom had visited the Huanan seafood market in Wuhan. The sequences had more than 99.98% sequence identity. In addition, they found that the nCoV-2019 genome had 88% identity to two bat-derived SARS-like coronaviruses, 79% identity to SARS-CoV, and only about 50% identity to another coronavirus that is a human pathogen—Middle Eastern respiratory syndrome (MERS-CoV). The team also found that nCoV-2019 had a similar receptor-binding domain structure to that of SARS-CoV. They write that “although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans.”
During the SARS-CoV outbreak in 2003, scientists and epidemiologists were true detectives, working to uncover which animal acted as the natural reservoir for the virus. In their search, they tested multiple animals, including hog badgers, Chinese hares, beavers, cats, and civets. The first results linked SARS to civet cats—a conclusion that lasted for about a year, until it was overturned by the discovery that bats carry coronaviruses. Indeed, further genomic analysis revealed that horseshoe bats are the true reservoir of SARS.
Given that the groundwork had been laid, finding the reservoir of nCoV-2019, a virus closely related to SARS, was a far shorter road to travel. And, the finding is not surprising. Since bats were shown to be the carrier of SARS in 2003, not only have many severe acute respiratory syndrome related coronaviruses (SARSr-CoV) been isolated from bats, the mammals have been recognized as the natural reservoir for over 100 other viruses including MERS, Ebola virus, Marburg virus, Hendra virus, and Nipah virus, to name a few.
Why do bats harbor and spread so many viruses? There are a few reasons that may contribute to this unique characteristic. As reviewed in the article, “Going batty: Studying natural reservoirs to inform drug development”, Wudan Yan noted that bats’ high-density lifestyle sets up a perfect storm of viral transmission. Another contributing factor may be the tremendous diversity in and among the bat species, which accounts for roughly 20% of all mammals. Also, bats fly, traveling with their viruses to more areas than most mammals. In addition, flight creates an increased innate immune response and body temperature, two other factors that may create the ability to host viruses that would kill other hosts.
Although several research groups have focused on studying the immune system of the bat, to understand how these animals carry viruses without succumbing to them, studying the bat immune system is still a nascent field. Indeed, the first bat genomes were published in 2013, by an international group that included BGI-Shenzhen, Novo Nordisk Foundation Center for Basic Metabolic Research, and the University of Copenhagen, Denmark. In 2016, the research group of Michelle Baker, PhD, a bat immunologist at Commonwealth Scientific and Industrial Research Organization (CSIRO) published findings in PNAS that bats’ immune systems are always turned on and have only three interferons—a fraction of the number of interferons found in people. At that time, Baker noted, “If we can redirect other species’ immune responses to behave in a similar manner to that of bats, then the high death rate associated with diseases, such as Ebola, could be a thing of the past.”
Baker tells GEN, “We have been working to try to understand how bats co-exist with viruses without disease and will be very interested to learn more about the role of bats in the emergence of 2019-nCoV.”