HKU Bulletin May 2008 (Vol. 9 No. 2)

15 RESEARCH The Pathway from Bats to a Pandemic Animals have been implicated in many of the emerging infectious disease of recent decades – from AIDS to Ebola – but could they also hold the key to averting a pandemic? S ince the outbreak of Severe Acute Respiratory Syndrome (SARS) in Hong Kong, in 2003, Professor Guan Yi , Professor in the Department of Microbiology, has had little more than the coronavirus on his mind. Like a latter day Philip Marlowe this fast- talking scientist has turned medical detective in his single-minded pursuit of first, the killer virus and, then, its source. He was the first to identify civet cats as the intermediate host and, in 2004, advised the People’s Republic of China Government to close the live animal markets in Southern China to avert a second SARS outbreak. Before SARS, relatively little was known about the evolutionary and ecological aspects of coronaviruses, most knowledge came from investigations involving disease in domestic animals and humans, rather than wild animals. So it was clear, that if a future SARS pandemic was to be averted, a lot of work had to be done. Guan’s years of dedicated research paid off recently with the publication of Evolutionary Insights into the Ecology of Coronaviruses, (in the Journal of Virology ), written in tandem with Professor of Microbiology, Malik Peiris, and other leading researchers. That paper finally revealed the Holy Grail of coronavirus research – the natural reservoir of the whole virus family. Guan, an expert in the ecology and evolution of influenza viruses and Director of the University’s State Key Laboratory of Emerging Infectious Diseases, credits philosophy and history in helping him draw the conclusions detailed in the paper: hailing it as the best research he has published since returning to HKU, from the US, over eight years ago. Several previous studies had suggested that horseshoe bats may be the source of the virus but no firm evidence had been presented to support the claim. So, in 2006, Guan and his team began looking at its prevalence in bats throughout Mainland China. It is commonly accepted that coronaviruses (the cause of the common cold) can infect a variety of animals including poultry, livestock and humans and, until recently they were classified into three groups. Guan’s research, which sampled 985 bats from 35 species in 15 provinces, found that bat coronaviruses mainly clustered in three different groups: group 1, another group containing all SARS and SARS-like coronaviruses (putative group 4) and an independent bat coronavirus group (putative group 5). “Because the bat so openly carries the coronavirus and because the virus in bats is so genetically diversified, (different bat species contain different coronaviruses even when they roost in the same cave) and because all the bats are free from disease we said maybe the bat is the natural reservoir for all coronaviruses after all. “We built up new knowledge – initially the coronavirus family was only separated into three groups. Then when we discovered this new information, we found that the three groups were not enough, so we created a new group system for coronavirus and the genetic information suggests that we are right. So, we proposed the natural reservoir, proposed a new group system, and proposed a new knowledge system for the virus.” The research was published in the August 2006 edition of the Journal of Virology . Armed with that knowledge Guan went on to establish that bats harbour a much wider diversity of coronoaviruses than any other animal species and that the lineage of their coronaviruses were older than in any other animal – dating back as far as the 17th century. Guan’s detailed research into the evolution of the virus was able to pinpoint the moments in history when it jumped the species barrier; for example, it first entered humans in 1941. “Then sixty years later we have SARS,” said Guan. “What happened in between? There is a huge information gap. This virus has not received much scientific attention, that’s why it took so long to recognise SARS. “We now know there have been repeated introductions from bats to other animals and occasionally coronaviruses have become established in other species. It looks like SARS was circulating for 10 to 20 years, in an unidentified host, before it caused the epidemic in 2003.” But the battle to avert a SARS pandemic is not over. Guan is still searching for the missing link – the creature that passed the SARS virus from bats to wild animals. “We don’t know how the virus got into the civet cats,” he said. “It may not have come directly from bats. This is just the beginning, the more research we do the more questions it raises. In a way we are writing the history of the coronavirus, but the intermediate host for SARS is still a mystery, it’s something we never found and until we can answer all the questions there are no guarantees that SARS will not re-emerge or cause the next pandemic.” 14