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. 2007;52(17):2374–2379. doi: 10.1007/s11434-007-0374-y

Genetic insight of the H5N1 hemagglutinin cleavage site

XiaoLi Guo 1, YiSheng Zhu 1,✉, YiXue Li 1, Ping Shi 1, HaoKui Zhou 1, JinSong Yao 1, ZhenDe Huang 1, DongQing Wei 1,✉
PMCID: PMC7089101  PMID: 32214726

Abstract

The cleavability of the hemagglutinin (HA) plays a major role in virulence of avian influenza viruses. Detailed analyses of the cleavage sequences and their evolution would give insights into the high pathogenicity of the H5N1 virus. HA segments were visually identifiable in the cellular automata (CA) image, and a feature gene segment (FGS) was only found in H5N1 rather than any other subtype. This FGS is a 30-bp gene segment mainly consisting of ‘A’ and ‘G’. When translated into amino acids the FGS converted into a sequence of mainly basic amino acids with positive charges. This feature amino acid segment (FAAS) was located in the cleavage site loop of HA which was potentially cleavable by various proteases. The 3D structure of H5N1 HA was reconstructed using homology modelling. It was found that the cleavage site loop was well exposed to potential proteases. The molecular surfaces were reconstructed to study how mutation and deletion of some amino acids in the FAAS affected the charge distribution. It was found that some mutations had severely changed the landscape of the charge distribution. Statistical analyses of FAAS were made with respect to when and where the H5N1 viruses were found. In 2005, there were less un-mutated FAAS than the other years according to temporal evolution, and more mutated FAAS appeared in China than other regions according to geographic distribution. These results are helpful for exploring the evolution of virus high pathogenicity.

Keywords: H5N1 hemagglutinin, cleavage site, cellular automata, feature amino acid segment, homology modelling

Footnotes

Supported by the Chinese National Key Research Program of Basic Sciences (Grant No. 2005CB724303), the National Natural Science Foundation of China (Grant No. 10376024), and the Tianjin Commission of Sciences and Technology (Grant No. 033801911)

Contributor Information

YiSheng Zhu, Email: yszhu@sjtu.edu.cn.

DongQing Wei, Email: dqwei@sjtu.edu.cn.

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Articles from Chinese Science Bulletin = Kexue Tongbao are provided here courtesy of Nature Publishing Group

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