[转移贴]-PLoS Pathog：甲型H5N1病毒在哺乳动物间传播分子机制

rojjer

xuyin 发表于5/1/2010 22:55

国际权威学术刊物《科学公共图书馆·病原》北京时间24日刊发的一篇文章称,最近,科学家们首次发现了决定H5N1禽流感病毒在哺乳动物之间水平传播的分子机制。

2003年以来,H5N1禽流感病毒已在15个国家感染400余人,致死率达60%。令人担忧的是,H5N1禽流感病毒每天都在进化和变异之中,如果获得在人群之间水平传播的能力,将导致灾难性后果。

调查表明,目前人类病例都是因为密切接触病毒感染的家禽或禽类产品所致。

中国国家禽流感参考实验室的科研人员利用豚鼠感染模型首次发现:病毒表面结构蛋白血凝素HA第160位氨基酸的突变,使H5N1禽流感病毒获得识别,并结合人类呼吸道上皮细胞受体的能力,与PB2基因701位点共同决定H5N1禽流感病毒在哺乳动物间的水平传播能力。据此,科研人员得以准确描述出决定H5N1在哺乳动物间传播的分子机制。

在此之前,该实验室科研人员已发现,PB2基因701位点对H5N1禽流感病毒感染哺乳动物的能力具有关键影响。

实验结果让科学家们振奋。"这意味着对H5N1禽流感病毒的研究取得重要进展。"陈化兰说,发现H5N1禽流感病毒在人群之间传播的关键分子机制,将有助于使相关防控措施更加科学和具有针对性。
PLoS Pathog 5(12): e1000709. doi:10.1371/journal.ppat.1000709

Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host

Yuwei Gao1,2, Ying Zhang1, Kyoko Shinya3, Guohua Deng1, Yongping Jiang1, Zejun Li1, Yuntao Guan1, Guobin Tian1, Yanbing Li1, Jianzhong Shi1, Liling Liu1, Xianying Zeng1, Zhigao Bu1, Xianzhu Xia2, Yoshihiro Kawaoka3,4,5*, Hualan Chen1*

1 Animal Influenza Laboratory of the Ministry of Agriculture and National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, People's Republic of China, 2 The 11th Institute, Academy of Military Medical Sciences, Changchun, People's Republic of China, 3 The International Center for Medical Research and Treatment, Kobe University, Kobe, Japan, 4 Division of Virology, Department of Microbiology and Immunology; International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan, 5 Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States of America

Since 2003, H5N1 influenza viruses have caused over 400 known cases of human infection with a mortality rate greater than 60%. Most of these cases resulted from direct contact with virus-contaminated poultry or poultry products. Although only limited human-to-human transmission has been reported to date, it is feared that efficient human-to-human transmission of H5N1 viruses has the potential to cause a pandemic of disastrous proportions. The genetic basis for H5N1 viral transmission among humans is largely unknown. In this study, we used guinea pigs as a mammalian model to study the transmission of six different H5N1 avian influenza viruses. We found that two viruses, A/duck/Guangxi/35/2001 (DKGX/35) and A/bar-headed goose/Qinghai/3/2005(BHGQH/05), were transmitted from inoculated animals to na?ve contact animals. Our mutagenesis analysis revealed that the amino acid asparagine (Asn) at position 701 in the PB2 protein was a prerequisite for DKGX/35 transmission in guinea pigs. In addition, an amino acid change in the hemagglutinin (HA) protein (Thr160Ala), resulting in the loss of glycosylation at 158–160, was responsible for HA binding to sialylated glycans and was critical for H5N1 virus transmission in guinea pigs. These amino acids changes in PB2 and HA could serve as important molecular markers for assessing the pandemic potential of H5N1 field isolates.