Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host.
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.
Gao
Yuwei
Y
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.
Zhang
Ying
Y
Shinya
Kyoko
K
Deng
Guohua
G
Jiang
Yongping
Y
Li
Zejun
Z
Guan
Yuntao
Y
Tian
Guobin
G
Li
Yanbing
Y
Shi
Jianzhong
J
Liu
Liling
L
Zeng
Xianying
X
Bu
Zhigao
Z
Xia
Xianzhu
X
Kawaoka
Yoshihiro
Y
Chen
Hualan
H
D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D006168:Guinea Pigs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000635:transmission*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics*
D000596:Amino Acids; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C502893:PB2 protein, influenza virus; D014764:Viral Proteins