Research reveals the molecular mechanism of H10N8 avian influenza virus infection in humans

Immunofluorescence staining of human hepatic tissue and duck small intestine tissue by HA protein

Following the important progress made in the inter-species communication study of H5N1 and H7N9 avian influenza viruses in 2013, the high-level research group of the Institute of Microbiology, Chinese Academy of Sciences, in the H10N8 avian influenza virus infected human Molecular Mechanisms and inter-species transmission new progress on trend assessment, research results have been published in the international journal "Nature communications" (Nature communications) online on January 9, 2015.

Since December 2013, three cases of human infection with H10N8 avian influenza virus have occurred in China, resulting in two deaths. Does this human-infected H10N8 virus have dual receptor-binding properties like the H7N9 virus, which can bind both human receptors and avian receptors? Is there a potential risk of large-scale proliferation?

In order to analyze the receptor binding specificity of this H10N8 virus, the researchers studied the receptor binding characteristics of the earliest isolate, Jiangxi Donghu strain H10N8 avian influenza virus, from the viral level and the HA protein level. The level of virus is also the level of HA protein, and H10 specifically binds to avian receptors, but does not have the ability to bind human receptors like the H7N9 Anhui strain. The researchers also used immunofluorescence to detect the binding ability of various HA proteins to human tracheal tissue and duck small intestine tissue, and proved that H10 protein has strong binding to duck intestinal tissue expressing avian receptors, but does not bind to expression. Human tracheal tissue of the source receptor (see figure below).

To elucidate the molecular mechanisms by which H10 proteins specifically bind to avian receptors, the researchers used structural biology methods to resolve the crystal structure of the H10 protein complex with avian receptors and human receptors. Structural analysis indicated that 137 arginine at the avian source receptor binding site plays a key role in the preferential binding of H10 to avian receptors.

The study showed that this human-infected H10N8 virus is still a typical avian influenza virus, and its affinity for human receptors is extremely weak, suggesting that the virus does not have the ability to spread in the population.

The research was completed by Dr. Wang Min, a doctoral student at the China Agricultural University, and Dr. Zhang Wei from the Institute of Microbiology. At the same time, the research work was also provided by Shi Yi of the Beijing Institute of Life Sciences of the Chinese Academy of Sciences, Li Xiangdong and Liu Jinhua of China Agricultural University, and Shu Yuelong and Zhou Jianfang from the Center for Viral Diseases of the Chinese Center for Disease Control and Prevention. The project was supported by funds from the Ministry of Science and Technology, the Natural Science Foundation and the Chinese Academy of Sciences.

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