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Mutations of two transmembrane cysteines of hemagglutinin (HA) from influenza A H3N2 virus affect HA thermal stability and fusion activity

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Abstract

Influenza A H3N2 virus caused 1968 Hong Kong influenza pandemic, and has since been one of the most prevalent seasonal influenza viruses in global populations, representing a credible pandemic candidate in future. Previous studies have established that the hemagglutinin (HA) protein is the predominant antigen and executes receptor binding and membrane fusion. Homologous sequence analysis of all HA subtypes of influenza viruses revealed that two cysteine residues (540 and 544) are uniquely present in the transmembrane domain (TM) of HA proteins from all influenza A H3N2 viruses. However, the functions of these two cysteines have not been fully studied. Here, we generated three mutants (C540S, C544L, and 2C/SL) to investigate the effects of the two TM cysteines on the biological functions of H3 HA. We herein presented evidences that the mutations of one or two of the cysteines did not affect the proper expressions of HA proteins in cells, and more importantly all mutant H3 HAs showed decreased thermal stability but increased fusion activity in comparison with wildtype HA. Our results taken together demonstrated that the two TM cysteines are important for the biological functions of H3 HA proteins.

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Acknowledgments

The authors would like to thank Dr. George Dacai Liu for critical review and revision of the manuscript.

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Authors and Affiliations

  1. State Key Laboratory of Biocontrol, Life Sciences School, Sun Yat-sen University, Guangzhou, 510006, People’s Republic of China

    Shun Xu, Jianqiang Zhou, Kang Liu, Qiliang Liu, Chunyi Xue, Xiaoming Li, Jing Zheng, Dongyu Luo & Yongchang Cao

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  1. Shun Xu
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  2. Jianqiang Zhou
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Correspondence to Yongchang Cao.

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Xu, S., Zhou, J., Liu, K. et al. Mutations of two transmembrane cysteines of hemagglutinin (HA) from influenza A H3N2 virus affect HA thermal stability and fusion activity. Virus Genes 47, 20–26 (2013). https://doi.org/10.1007/s11262-013-0924-0

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  • DOI: https://doi.org/10.1007/s11262-013-0924-0

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