Changes in the Length of the Neuraminidase Stalk Region Impact H7N9 Virulence in Mice

Yuhai Bi; Haixia Xiao; Quanjiao Chen; Yan Wu; Lifeng Fu; Chuansong Quan; Gary Wong; Jun Liu; Joel Haywood; Yingxia Liu; Boping Zhou; Jinghua Yan; Wenjun Liu; George F Gao

doi:10.1128/JVI.02553-15

Changes in the Length of the Neuraminidase Stalk Region Impact H7N9 Virulence in Mice

J Virol. 2015 Dec 9;90(4):2142-9. doi: 10.1128/JVI.02553-15. Print 2016 Feb 15.

Authors

Yuhai Bi¹, Haixia Xiao², Quanjiao Chen³, Yan Wu⁴, Lifeng Fu⁴, Chuansong Quan⁵, Gary Wong⁴, Jun Liu⁶, Joel Haywood⁴, Yingxia Liu⁷, Boping Zhou⁷, Jinghua Yan⁴, Wenjun Liu⁸, George F Gao⁹

Affiliations

¹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China Center for Influenza Research and Early Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China beeyh@im.ac.cn gaof@im.ac.cn.
² Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China Center for Influenza Research and Early Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China.
³ CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Hubei, China Center for Influenza Research and Early Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China.
⁴ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
⁵ National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
⁶ Center for Influenza Research and Early Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
⁷ Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China.
⁸ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Center for Influenza Research and Early Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China.
⁹ CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China Laboratory of Protein Engineering and Vaccines, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China Center for Influenza Research and Early Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, Zhejiang University, Hanzhou, China Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China beeyh@im.ac.cn gaof@im.ac.cn.

Abstract

The neuraminidase stalk of the newly emerged H7N9 influenza virus possesses a 5-amino-acid deletion. This study focuses on characterizing the biological functions of H7N9 with varied neuraminidase stalk lengths. Results indicate that the 5-amino-acid deletion had no impact on virus infectivity or replication in vitro or in vivo compared to that of a virus with a full-length stalk, but enhanced virulence in mice was observed for H7N9 encoding a 19- to 20-amino-acid deletion, suggesting that N9 stalk length impacts virulence in mammals, as N1 stalk length does.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Body Weight
Cytokines / analysis
Histocytochemistry
Influenza A Virus, H7N9 Subtype / genetics*
Influenza A Virus, H7N9 Subtype / pathogenicity*
Lung / pathology
Lung / virology
Mice, Inbred BALB C
Neuraminidase / genetics*
Orthomyxoviridae Infections / pathology
Orthomyxoviridae Infections / virology*
Sequence Deletion
Viral Load
Viral Proteins / genetics*
Virulence
Virulence Factors / genetics*

Substances

Cytokines
Viral Proteins
Virulence Factors
NA protein, influenza A virus
Neuraminidase