H4 substation influenza virus hemocoagulant protein from binding to human source receptor adaptation of the molecular basis.

The team of academician Gao Fu, a member of the Chinese Academy of Sciences and vice president of the Beijing Institute of Life Sciences of the Chinese Academy of Sciences, has made new and important progress in the molecular mechanism of H4 sub-avian influenza virus adapting to human beings and in the prediction of early warning of interseedan transmission. the results of the
study were published online August 1st in the international academic journal Cell Reports under the title Avian-to-Human Receptor-Binding by Influenza A Virus Hemagglutin H4 (the molecular basis for H4 sub-influenza virus hemagglutininin protein from binding poultry to human receptor adaptation).
H4 sub-influenza virus is widely distributed in wild birds and poultry and is widely prevalent in many countries and regions in Asia, Europe and North America.
In recent years, different genotypes of H4 sub-influenza virus in China's central, eastern and southern China common epidemic, H4 sub-influenza virus between the mixed re-emergence and H4 sub-type and other sub-types such as H3 sub-influenza virus re-emergence incidents occur frequently, resulting in ducks carrying complex H4 sub-influenza virus.
In addition to infected birds, H4 sub-influenza virus has been isolated in mammals such as seals and pigs, especially in Canada in 1999 isolated two pig-sourced H4N6 strains on HA Q226L and G228S mutations, whether these swine-sourceD H4N6 influenza virus has begun to adapt to the combination of human receptors, whether there is a risk of human transmission, is an urgent scientific question to be answered.
To this end, the researchers selected two H4 sub-influenza virus representative strains, including avian-isolated strains (A/duck/Czech/1956, Avian-H4N6) and pig isolated strains (A/swine/Ontario/01911?1/99, Swine-H4N6) to assess the molecular mechanisms of the transition of the receptor binding characteristics of the H4 subtoxic coagulation protein HA.
experiments with virus ELISA, surface plasma resonance SPR, tissue immunofluorescence staining, and other experiments, the researchers found that the bird isolated strains specific to bind to the bird receptor rather than the human receptor, while the pig isolated strain preferred to bind to the human receptor. The
mutation experiment shows that the mutation of G228S/A can make HA obtain the binary binding characteristics, and shows that the G228S/A mutation is very important for the virus from the stage of "preference binding poultry receptor" to obtaining "double receptor binding characteristics", while the Q226L mutation can make HA completely realize the transformation of receptor binding characteristics from binding bird receptor to binding human receptor, and is the most critical amino acid to achieve complete adaptation to human receptor binding.
To further clarify the molecular mechanism of H4 HA adaptation to human beings, the researchers used structural biology to analyze the crystal structure of H4 and the compounds of different mutants and receptaminants, and to interpret the molecular mechanism of the transformation of their receptamination binding characteristics structurally.
The study found that the pig isolated H4 sub-avian influenza virus with Q226L and G228S mutations already has the characteristics of pandemic recepor binding, and expounded the molecular mechanism of H4 sub-avian influenza virus adapted to human beings, which provided a theoretical basis for the monitoring and early warning prediction of H4 sub-avian influenza virus.
Gaofu research team Song Hao as the first author of the article, Gao Fu as the author of the newsletter.
research has been supported by the Chinese Academy of Sciences, the Ministry of Science and Technology, the National Natural Science Foundation of China, etc.
.