HKU Bulletin June 2011 (Vol. 12 No. 2)

Scientists in the Department of Microbiology have made two major breakthroughs that could change the face of influenza treatment. In a study, published in Nature Biotechnology , the team led by Professor Yuen Kwok-yung, discovered that an important viral structural protein - influenza nucleoprotein (NP) - can be used as a target to kill flu viruses, including H1N1, H3N2 and H5N1. This is the first time that research work from the HKSAR led by local researchers has been published in Nature Biotechnology , the top journal in this field. Yuen, Henry Fok Professor in Infectious Diseases, Head of the Department of Microbiology, HKU Li Ka Shing Faculty of Medicine says, "From conceiving the idea, designing the study, to carrying out the experiments, almost everything was done here in Hong Kong by local researchers. It shows that Hong Kong has the capability to develop and lead world-class basic science research. The research was not surveillance type work but a conceptual breakthrough. We are truly proud of it." Fighting flu head-on With the alarming rise in resistance of flu viruses to anti-viral drugs this new discovery provides fresh hope that the medical establishment can continue to fight flu and severe influenza pneumonia head on. Professor Yuen explains, "For many years, antiviral drugs have often been directed towards viral enzymes which catalyse the viral life cycle so as to reduce the viral load in patients. By reducing the number of viruses produced, for example in influenza, by administering antiviral drugs, the immune system will sooner or later control the infection." "Alternatively, some antiviral drugs act on the surface proteins of the virus to stop it from attaching or entering the host cell. This is also another important way to control viral infections. But our Nature Biotechnology paper shows for the first time that an internal (non-surface) structural (non-enzyme) protein of influenza virus can be effectively targeted by a novel antiviral compound. That is, we are attacking the heart (nucleoprotein) of the influenza virus." "If this can happen for influenza viruses, then antiviral agents can be found for any virus with an internal nucleoprotein. This represents a very important breakthrough in our concept of antiviral targeting and opens up a new arena for antiviral discovery. This can help to address the problem of antiviral resistance by creating a new class of antiviral compounds." He was assisted in his research by co-principal investigator Dr Richard Kao of the Carol Yu Centre for Infection in the Department of Microbiology and in collaboration with Professor Yang Dan, Morningside Professor in Chemical Biology of the Department of Chemistry. Reducing mortality In another study, also led by Professor Yuen, it was found that treating patients with convalescent plasma from donors who have recovered from swine flu can reduce the mortality rate in the most severe cases. From April to December 2009, more than 30,000 patients were found to have contracted the human swine influenza H1N1 in Hong Kong. Among them, one per cent shows symptoms severe enough to require hospitalization and respiratory support. Eighty-five of those patients eventually died. That same year the large-scale human swine flu vaccination programme targeting high-risk sections of the population was launched by the Department of Health in Hong Kong, but uptake rate was unfortunately very low due to a reported case of Guillain-Barre syndrome following vaccination in a health care worker. Also, a significant proportion of the patients infected with swine flu were healthy young adults with no apparent risk factors, and therefore not candidates for vaccination. Many of these severe cases were late presenters who failed to receive treatment within the optimal 48-hour period for successful treatment with antiviral agents like Tamiflu. Working with Dr Ivan Hung Fan-ngai, Clinical Assistant Professor of the Department of Medicine, Professor Yuen treated these severe cases with convalescent plasma. Neutralizing antibodies Professor Yuen says, "Anti-flu drugs like Tamiflu or Relenza are quite effective in treating flu within two days of the onset of symptoms. However, patients with severe influenza pneumonia often come to the hospitals after five days, so antiviral treatment is not very useful in this group of late presenters." "The neutralizing antibodies in the convalescent plasma of recovered patients do not suffer the same shortcomings seen in Tamiflu and Relenza. We found that the survival rate of patients given convalescent plasma is double that of patients not given such treatment." "The treatment effectively reduces the viral load and dampens the pro-inflammatory cytokine response, resulting in reduced mortality. It also overcomes the problems of the emergence of resistant strains and of late presenters." Professor Yuen says they will continue to investigate exactly why antibodies appear to be superior to antiviral drugs in young late-presenting patients. The results of this project were published in the journal Clinical Infectious Diseases . Professor Yuen Kwok-yung Research 21 June 2011 New Weapons to Beat an Age-Old Killer Two groundbreaking studies could change the way lethal flu viruses are combated in the future.