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Microbiol Spectr. 2021 Dec 22;9(3):e0143921. doi: 10.1128/spectrum.01439-21. Epub 2021 Dec 22.

Identification of Hemagglutinin Mutations Caused by Neuraminidase Antibody Pressure.

Microbiology spectrum

Fei Wang, Zhimin Wan, Yajuan Wang, Jinsen Wu, Hui Fu, Wei Gao, Hongxia Shao, Kun Qian, Jianqiang Ye, Aijian Qin

Affiliations

  1. Ministry of Education Key Laboratory for Avian Preventive Medicine, Yangzhou Universitygrid.268415.c, Yangzhou, Jiangsu, China.
  2. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, China.
  3. Joint International Research Laboratory of Agriculture and Agri-Product Safety of Ministry of Education of China, Yangzhou Universitygrid.268415.c, Yangzhou, Jiangsu, China.

PMID: 34937172 PMCID: PMC8694115 DOI: 10.1128/spectrum.01439-21

Abstract

The balance in the functions of hemagglutinin (HA) and neuraminidase (NA) plays an important role in influenza virus genesis. However, whether and how N2 neuraminidase-specific antibodies may affect the attributes of HA remains to be investigated. In this study, we examined the presence of amino acid mutations in the HA of mutants selected by incubation with N2-specific monoclonal antibodies (MAbs) and compared the HA properties to those of the wild-type (WT) A/Chicken/Jiangsu/XXM/1999 (XXM) H9N2 virus. The higher NA inhibition (NI) ability of N2-specific MAbs was found to result in greater proportions of mutations in the HA head. The HA mutations affected the thermal stability, switched the binding preferences from α2,6-linked sialic acid receptor to α2,3-linked sialic acid receptor, and promoted viral growth in mouse lungs. These mutations also caused significant HA antigenic drift as they decreased hemagglutination inhibition (HI) titers. The evolutionary analysis also proved that some HA mutations were highly correlated with NA antibody pressure. Our data demonstrate that HA mutations caused by NA-specific antibodies affect HA properties and may contribute to HA evolution.

Keywords: antigenic drift; hemagglutinin mutations; influenza virus; neuraminidase antibody pressure; receptor binding preferences

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