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

PLoS Pathogens

Zejun Li¹  Xianzhu Xia¹  Yongping Jiang¹  Yuntao Guan¹  Jianzhong Shi¹  Kyoko Shinya¹  Xianying Zeng¹  Yanbing Li¹  Guobin Tian¹  Liling Liu¹  Zhigao Bu¹  Yuwei Gao¹  Ying Zhang²  Yoshihiro Kawaoka²  Guohua Deng³  Hualan Chen³ 

[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;The 11th Institute, Academy of Military Medical Sciences, Changchun, People's Republic of China;The International Center for Medical Research and Treatment, Kobe University, Kobe, Japan

关键词: H5N1;    Guinea pigs;    Influenza viruses;    Viral replication;    Viral transmission;    infection;    Avian influenza;    Microbial mutation;    Glycosylation;   

DOI  :  10.1371/journal.ppat.1000709

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 naïve 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.

【 授权许可】

CC BY