Research On The Evolution And Transmission Of Avian Influenza Virus

Avian influenza virus is a kind of influenza A virus.In recent years,more and more subtypes of avian influenza viruses have obtained the ability to cross the host and infect human beings.Among them,H7N9 subtype avian influenza virus and H5N1 subtype avian influenza virus outbroke frequently in human society,which have brought more and more threat to human life and safety.In particular,the fifth outbreak of H7N9 virus in China have caused the most serious damage and the number of infections was close to the sum of the four previous outbreaks.This not only brought panic to human society,but also caused huge economic losses.In addition,studies have shown that H9N2 subtype avian influenza virus has been widely worldwide spreading,and also frequently producing new subtype avian influenza virus with reassortment.In this way the new-type avian influenza virus can often obtain the ability from the H9N2 virus to cross the host and infect human beings.Therefore,in order to effectively cope with the potential threat brought by the rapid evolution of avian influenza virus,we need to monitor the genetic variation of avian influenza in a timely manner.We have carried out a systematic study of a variety of subtype avian influenza viruses,focusing on the scientific problems of the evolution and transmission of avian influenza virus.The first part of this work,we take the fifth epidemic of H7N9 subtype avian influenza virus as the starting point.Through phylogenetic analysis,the codon usage bias analysis and other analyses,for the first time we found that virus in the fifth epidemic used the different codon usage bias and had different genetic evolution characteristics compared with the previous epidemics.In HA gene segment,the evolution rate in fifth outbreaks is the highest,and the virus in the HA gene not only has 327 K,328R,329 T and 330 A four amino acid insertion which caused the emergence of highly pathogenic strains,also has new amino acid mutations like R58 L,E115R,A123 P,K173E,V186 I,G326R,E395 K and V422 M.In addition,we have tracked the dynamic changes in the genetic characteristics of the H7N9 subtype avian influenza virus.In combination with other results,we infer that the fourth epidemic and the fifth epidemic have formed a "two-step" evolution process,in the first step of which the virus has completed the evolution of the NA gene with high rate of evolution through the fourth epidemic,then in the second step,the virus has inherited NA gene segment evolution after the first step and continued to complete the evolution of HA gene in the fifth epidemic.In addition,we found that the reassortment between the H7N9 virus and the H9N2 virus occurred in each epidemic.So,in the second part of this article,we have shifted the focus to the H9N2 subtype of avian influenza virus.We first divided the H9N2 virus into several groups according to the phylogenetic reconstruction results and then used the phylogeography analysis to establish the whole World transmission networks of the H9N2 virus.In the study,we found that the H9N2 subtype avian influenza virus evolved three species with independent evolution process,specific geographic area and different genetic characteristics.According to the geographic spreading range,we named the species as “Worldwide lineage” “Asia-Africa lineage” and “China lineage”.Through the research we found that each lineage has independent transmission line and the mode of communication.The main transmission source of “Worldwide lineage |” was the migratory birds.“Worldwide lineage” has the largest regional spread area,and the minimum positive selection pressure.The origin of the “Worldwide lineage” is the United States,and the transmission centers are including the Hongkong,Japan,South Korea,Holland and mainland China.The main transmission source of “Asia-Africa lineage” is both from the migratory birds and the poultry trade.“Asia-Africa lineage” has spread across the Asia and Africa,and the positive selection pressure is in the medium level.The origin of propagation is Japan.The main communication centers are Pakistan and Iran.The main driving force of "China lineage" is poultry trade.The virus in the “China lineage” has the smallest transmission area and the largest positive selection pressure.The origin of the spread is Guangdong province and Hongkong,China.The main communication centers are the Pearl River Delta and the Yangtze River Delta.In addition,combined with the evolution and transmission rules of different groups and the results of common ancestor divergence time of different populations,we first proposed the H9N2 global subtype avian influenza virus that has such a "global sowing,regionally adaptive evolution" propagation and evolution mode.In the third part of this article,we calculate the coevolution model of the key subtypes avian influenza virus with the method of CO mutation calculation.The current evolution of avian influenza virus is mostly focused on a certain segment of the gene or some amino acid mutation sites.There is a lack of research on the synergistic mutation and coevolution of different amino acid mutation sites,different segments of the gene segments.The H7N9 subtype of avian influenza virus,H9N2 subtype avian influenza virus,and H5N1 subtype avian influenza virus are analyzed to find out the co-evolution amino acid mutation between all 8 segments.And then we draw the co-evolutionary relationship between each gene segment.We found that H7N9 subtype and H5N1 subtype avian influenza virus had 5 combinations of amino acid co-mutation sites,while the H9N2 subtype avian influenza virus had 11 groups of amino acid mutation sites.In addition,there are some co-evolution relationships between H5N1 subtype avian influenza virus at some gene stages,but there is almost no co-evolution relationship between H7N9 subtype avian influenza and H9N2 subtype avian influenza virus.Through the study of the evolution process of H7N9 subtype avian influenza virus,the study of the global spread networks of avian influenza virus H9N2 subtype avian influenza virus and the study of co-evolution model in the key subtypes avian influenza virus,we have further revealed the characteristics and laws of the avian influenza virus presents in the evolution and propagation process.The research results not only deepen the understanding of the evolution and transmission of avian influenza virus,but also have guidance value for the prevention and control and monitoring of influenza virus.