HKU Bulletin April 2006 (Vol. 7 No. 2)

22 Research into H5N1 Virus Continues Apace BATTLE AGAINST BIRD FLU L eading bird flu scientists have been awarded a $4.6 million grant to continue their research into the lethal H5N1 virus. Professor Malik Peiris, of the Department of Microbiology, who is the coordinator of the project and his team secured the grant via the Hong Kong Research Grants Council’s Central Allocation Vote (CAV) programme. This will allow them to collaborate with experts from the Hong Kong University of Technology (HKUST) and City University of Hong Kong. Peiris said: “A big part of the team is here at HKU and the work builds on the existing excellence in avian flu research that has been built up at HKU since the 1970s by Professor Ken Shortridge. “Since bird flu hit Hong Kong in 1997 that work has expanded dramatically. Since then Dr Y. Guan, Dr L.L.M. Poon, Dr H.L. Chen, Professor K.Y. Yuen and myself have all been involved in studies on aspects of influenza and H5N1 disease.” Initially, research involved the surveillance and molecular evolution of avian influenza viruses, including the H5N1 virus. But more recently the team has started looking at the pathogenesis of human disease to uncover how the virus causes such a severe disease. “The recent grant was awarded to build on previous research findings,” said Peiris. “In 2002 a paper published in The Lancet compared the responses of human cells to H5N1 virus and to normal flu viruses to try and see the difference between them. “We were excited to find that H5N1 viruses differ from the common human flu virus in the cellular pathways that they activate,” he said. These collaborative studies between the Department of Microbiology and the Department of Paediatrics and Adolescent Medicine (with Chair of Paediatrics Professor Lau and Associate Professor Dr Allan Lau Sik Yin) at the University have been further extended with publication last year in the online medical journal, Respiratory Research . Other publications are also in the pipeline. Overall, these studies suggest that the virus causes the immune system’s cytokines and chemokines to overract, sometimes aggravating the disease process. This explains why H5N1 can kill healthy young children and adults, unlike the common human flu which causes problems mainly at the extremes of age. “The CAV programme will take that research to a much deeper level,” said Peiris. “We are now extending the existing collaborations within HKU to involve Professor Nancy Ip and her team at HKUST and Professor Michael Yang at City University to unravel the mechanisms of the H5N1 disease causation in humans. “As part of this study we are also looking at the genetics of the virus from Indonesia and Vietnam – that’s the core principal investigator, Dr Guan’s area – and, of course, we are also collaborating with scientists in Indonesia and Vietnam on these studies,” he said. Meanwhi le, a more recent paper publ ished in the Proceedings of the National Academy of Sciences of the United States of America by Dr Guan and an international team of 28 researchers from across the region and the United States, suggests that wider surveillance than previously thought may be required to control the outbreak of avian flu and prepare for a possible bird flu pandemic. The researchers identified several different sub-lineages of the bird flu virus from normal migratory birds and poultry across Asia. Associate Professor Dr Guan Yi said: “Since the initial outbreak of H5N1 from geese in southern China in 1996, the virus has expanded its range across Southeast Asia, periodically causing human disease but just how H5N1 has perpetuated across the region has remained unclear.” However, the research team frequently found H5N1 virus in migratory birds as well as in market poultry populations across Asia during their influenza surveillance. “Genetic analysis showed that distinct branches of the virus have become established in different geographical regions. Although the findings show that H5N1 can be transmitted over long distances in migratory birds, the transport of infected poultry appears to be the main mechanism of H5N1 spread in Asia. “More importantly, the majority of positive samples analysed in this study came from poultry that showed no sign of the disease. This may have important implications for the planning of future surveillance which will need to encompass healthy poultry as well.” Such genetic diversity may also have implications for the development of human vaccines for bird flu. “The research suggests that surveillance of H5N1 should be broad-based in geographical terms to encompass a wide variety of genetic variants so that we can select appropriate vaccine candidates,” he said. Battle Against Bird Flu Associate Professor Dr Guan Yi 23