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Mouse lung‐adapted mutation of E190G in hemagglutinin from H5N1 influenza virus contributes to attenuation in mice

Identifieur interne : 000615 ( Main/Exploration ); précédent : 000614; suivant : 000616

Mouse lung‐adapted mutation of E190G in hemagglutinin from H5N1 influenza virus contributes to attenuation in mice

Auteurs : Pengfei Han [République populaire de Chine] ; Yi Hu [République populaire de Chine] ; Wei Sun [République populaire de Chine] ; Sen Zhang [République populaire de Chine] ; Yuchang Li [République populaire de Chine] ; Xiaoyan Wu [République populaire de Chine] ; Yinhui Yang [République populaire de Chine] ; Qingyu Zhu [République populaire de Chine] ; Tao Jiang [République populaire de Chine] ; Jing Li [République populaire de Chine] ; Chengfeng Qin [République populaire de Chine]

Source :

RBID : ISTEX:B3ACC6CB74E03A31AD78DEECF543785DA5D9C4FD

Abstract

The highly pathogenic H5N1 avian influenza virus is one of the greatest influenza pandemic threats since 2003. The association of the receptor binding domain (RBD) with the virulence of influenza virus is rarely addressed, particularly of H5N1 influenza viruses. In this study, BALB/c mice were intranasally infected with A/Vietnam/1194/2004 (VN1194, H5N1). The mouse lung‐adapted variants were isolated and the mutation of E190G (H3 numbering) in the RBD was recognized. The recombinant virus, rVN‐E190G carrying E190G in hemagglutinin (HA) was designed and rescued using reverse genetics techniques. The receptor binding activity, growth curve and pathogenicity in mice of the rVN‐E190G were investigated. Results demonstrated that rVN‐E190G virus increased the binding avidity to α2,6 SA (sialic acid) and reduced the affinity to α2,3 SA, meanwhile weakened the viral replication in vitro. Moreover, the virulence assessment demonstrated that rVN‐E190G was attenuated in mice. These results indicated that the mutation E190G in HA decreases H5N1 viral replication in vitro and significantly attenuates virulence in vivo. These findings identify one of the determinants in RBD which can be associated with H5N1 virulence in mice. J. Med. Virol. 87:1816–1822, 2015. © 2015 Wiley Periodicals, Inc.

Url:
DOI: 10.1002/jmv.24257


Affiliations:


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<div type="abstract" xml:lang="en">The highly pathogenic H5N1 avian influenza virus is one of the greatest influenza pandemic threats since 2003. The association of the receptor binding domain (RBD) with the virulence of influenza virus is rarely addressed, particularly of H5N1 influenza viruses. In this study, BALB/c mice were intranasally infected with A/Vietnam/1194/2004 (VN1194, H5N1). The mouse lung‐adapted variants were isolated and the mutation of E190G (H3 numbering) in the RBD was recognized. The recombinant virus, rVN‐E190G carrying E190G in hemagglutinin (HA) was designed and rescued using reverse genetics techniques. The receptor binding activity, growth curve and pathogenicity in mice of the rVN‐E190G were investigated. Results demonstrated that rVN‐E190G virus increased the binding avidity to α2,6 SA (sialic acid) and reduced the affinity to α2,3 SA, meanwhile weakened the viral replication in vitro. Moreover, the virulence assessment demonstrated that rVN‐E190G was attenuated in mice. These results indicated that the mutation E190G in HA decreases H5N1 viral replication in vitro and significantly attenuates virulence in vivo. These findings identify one of the determinants in RBD which can be associated with H5N1 virulence in mice. J. Med. Virol. 87:1816–1822, 2015. © 2015 Wiley Periodicals, Inc.</div>
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