Mechanism of the transmission of highly pathogenic avian influenza virus to humans and the prevention of pandemic

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H5N1 highly pathogenic influenza viruses (HPAIV) have spread to numerous countries in Asia, Europe and Africa infecting not only large numbers of poultry, but also an increasing number of humans, often with lethal effects. The aim of this project is to elucidate the molecular mechanism of transmission of HPAIV into humans and to prevent the emerging of pandemic in human world. The results of our project in last 2 years are summarized as follows: 1. Some of the HPAIV (H5N1 subtype) isolated from humans in China and Vietnam in 2003 and 2005 has already mutated into human type which recognize human receptor (sialic acid2-6Gal sugar chains), and may be able to transmit from human to human. 2. Tamiflu (anti-influenza drug)-resist HPAIV has been firstly isolated from the Vietnam patient who treated with prophylactic dose of Tamiflu. 3. We succeeded to prepare high amount of sialyltransferase (ST6Gal) which make Neu5Ac2-6Gal receptor for human influenza viruses. We also found that the cells highly expressed ST6Ga1 enhanced the infection of human influenza viruses. 4. Mutations at position of 182 and 192 independently convert the hemagglutinin (HA) of H5N1 viruses known to recognize the avian receptor to ones that recognize the human receptor. 5. We found that both bird and human receptor, Sialic acid 2-3(6)Gal sugar chains are present in the chicken and quail intestines, indicating that these animals may have a role as the intermediate hosts for the transmission of HPAIV from poultry to humans. 6. We developed the simple and sensitive technique to detect the mutation of HPAIV from bird type to human type which spread easily from human to human and emerge the pandemic in human world. This method may be useful to survey the molecular signals of HPAIV mutation for the adaptation to humans.