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

高致病性禽流感病毒人传人机制及大流行的预防

基本信息

批准号：
17390022
负责人：
SUZUKI Yasuo
金额：
$ 9.02万
依托单位：
Chubu University (2006)University of Shizuoka (2005)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

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.

H5N1高度致病的流感病毒（HPAIV）已经传播到亚洲，欧洲和非洲的许多国家，不仅感染了大量家禽，而且还越来越多的人类感染了人类，通常会产生致命的影响。该项目的目的是阐明HPAIV向人类传播的分子机制，并防止人类世界中大流行的出现。过去两年中我们项目的结果总结如下：1。从2003年和2005年，从中国和越南在中国和越南分离的一些HPAIV（H5N1亚型）已经突变为识别人类受体（唾液酸2-6gal糖链），并可能从人传播到人类。 2。tamiflu（抗炎性药物） - 抗药性HPAIV首先是从越南患者中分离出来的，该患者用tamiflu的预防剂量治疗。 3。我们成功地准备了大量的辅助转移酶（ST6GAL），该酶是人类流感病毒的NEU5AC2-6GAL受体。我们还发现，高度表达的ST6GA1细胞增强了人类流感病毒的感染。 4。在182和192位置的突变独立转化了已知的H5N1病毒的血凝素（HA），已知可以识别鸟类受体，以识别识别人体受体的受体。 5。我们发现鸡和人体受体，唾液酸2-3（6）gal糖链都存在于鸡和鹌鹑肠中，表明这些动物可能是将HPAIV从家禽传播到人类传播的中间宿主的作用。 6。我们开发了一种简单而敏感的技术，以检测HPAIV从鸟类类型到人类类型的突变，该突变从人类到人类，并在人类世界中流行。该方法可能有助于调查适应人类的HPAIV突变的分子信号。