HKU Bulletin November 2009 (Vol. 11 No .1)

15 November 2009 Research THE RACE IS ON TO AVERT a new pandemic New research takes HKU scientists one step closer to potentially eliminating future influenza pandemics. “Hong Kong’s flu group (an Area of Excellence team comprising over 30 researchers across four universities) is now entering a new phase,” he says. “We already know where the viruses that triggered the last pandemics came from, how they were generated and which pathway they took, we are now putting all our energy, all our manpower and finance towards one end, and maybe we will have a chance to avert the next pandemic. So this is very good.” However, it was not until retired pathologist Johan Hultin retrieved preserved lung tissue from a female body buried in permafrost in an Alaskan village that Taubenberger was able to complete the whole genome. Between 1997 and 2005 the Taubenberger team was able to sequence the entire genome of the 1918 Spanish Flu virus, publishing their findings in top scientific journals. “But,” says Professor Guan, “each time they interpreted the findings incorrectly. They kept saying it was from an avian source and had jumped directly to humans. This became an indisputable truth and this concept misled scientists for years.” Guan credits his two mentors – Robert Webster and former HKU Professor, Ken Shortridge – with teaching him to trust his own intuition and to question the accepted wisdom, helping him see beyond the so- called ‘indisputable truth’ to establish this new breakthrough. Meanwhile, further research shows that the current swine flu virus – a H1N1 virus that has the potential to cause the 21st century’s first influenza pandemic – may have been circulating in humans since January this year, several months before the outbreak in Mexico was first detected. A multi-University team, again led by Professor Guan and Dr Smith along with Dr Andrew Rambaut, of the University of Edinburgh, has shown that the virus circulated in swine for at least ten years before leaping the species barrier. The results, published in the journal Nature , highlight the need for systematic surveillance of influenza swine and provide evidence that new genetic elements in pigs can result in the emergence of viruses with pandemic potential in humans. Professor Guan says that despite the widespread surveillance of influenza viruses in humans in recent years, the lack of a systematic surveillance in swine has allowed the undetected persistence and evolution of the potentially deadly strain. Scientists in the Department of Microbiology are piecing together a jigsaw puzzle that is rewriting the evolutionary history of influenza viruses and may, ultimately, succeed in averting future flu pandemics. Led by Professor Guan Yi and Dr Gavin Smith, of the State Key Laboratory of Emerging Infectious Diseases in the Li Ka Shing Faculty of Medicine, the research turns previously held convictions on their head by showing that the three worst influenza outbreaks of the 20th century (1918, 1957 and 1968) did not emerge suddenly, as previously thought, but circulated in either swine or humans for years before triggering the pandemics. The research also asserts that these viruses did not jump directly from birds to human – as previously thought – but from pigs. In particular, the H1N1 virus which caused the 1918, Spanish Flu, and went on to kill an estimated 50 million people worldwide, was most likely generated by genetic exchanges between swine and human viruses. Staggeringly, these virus genes appear to have been in humans for between two and 15 years before triggering the pandemic. Similarly, the H2N2 virus which caused the 1957 pandemic seems to have been in the human population for up to seven years before the pandemic took off. And likewise the H3N2 virus implicated in the 1968 Hong Kong flu appears to have been around for up to five years before the pandemic started. The research, published in the prestigious Proceedings of the National Academy of Sciences (PNAS) , raises fresh concerns about the current swine flu virus circulating the globe and suggests that surveillance of influenza viruses in humans should be altered to consider all virus genes not just two – the HA and NA viruses. Professor Guan says: “This turns earlier research on its head, it rewrites history and the impact will be long felt. By correcting a historical mistake we may have changed the impact of future pandemics.” He added that the results of this large-scale evolutionary study were possible thanks to the use of a new methodology – an advanced molecular clock method – which was employed to estimate the time at which each gene of the pandemic influenzas was introduced to humans. “But now we need to identify the key knowledge gap in the field. What is that knowledge gap? Well nobody can tell you when an influenza virus will mutate to become a mature pandemic virus.” Indeed, knowledge of the viruses that caused the three 20th century pandemics was sketchy throughout most of the last century. “When the 1918 Spanish Flu pandemic happened they didn’t even know what the virus was. It was not identified until 1930 when it was isolated from pigs, and then from humans three years later,” explains Professor Guan. A fragment of the virus that caused the Spanish Flu was not isolated until 1997 when Dr Jeffrey Taubenberger, from the US Armed Forces Institute of Pathology, started to screen preserved tissue samples from 1918 influenza victims.