Comparison Of Antigenic And Genetic Evolution Of Human Influenza A Viruses In Shanghai Area In Recent Years And Identifying Potential Immunodominant Positions Of Human Influenza A/H1N1 Viruses

Influenza is a highly contagious acute respiratory disease which was caused by influenza virus. Because of high genetic variation of the virus, it infected the population again and again with high incidence. Antigenic evolution map and genetic evolution map were used to visualize antigenic and genetic evolution of human influenza A/H1N1 and A/H3N2 viruses in Shanghai area in recent years. Potential immunodominant positions of human influenza A/H1N1 viruses were identified and bioinformatics models for predicting antigenic variants of human influenza A/H1N1 viruses were proposed.The details as follow:1. Antigenic evolution map and genetic evolution map of human influenza A/H1N1 and A/H3N2 viruses in Shanghai area in recent years were constructed. The results showed that strains of influenza A/H3N2 viruses from 2007 to 2008 were gathered together according to the year in the antigenic evolution map and genetic evolution map. There existed cross protection between some strains from 2007 and 2008. The mutation at the amino acid position 194 makes vaccine may not provide a effective protective immunity. The results also showed that strains of influenza A/H1N1 viruses from 2005 to 2008 were gathered together according to the year in the antigenic evolution map and genetic evolution map. The mutation at the amino acid position 140 may be responsiable for the antigenic variation of influenza A/H1N1 viruses in Shanghai area in recent years. There existed cross protection between some strains, which shows that influenza A/H1N1 viruses evolve relatively slowly in Shanghai area in recent years. The cross protection between A/Shanghai/MH79/2008 and A/Brisbane/59/2007 was feeble, which should arouse our attention.Antigenic prediction models of human influenza A/H3N2 viruses were implemented to predict antigenic distances based on the differences of amino acid sequences. Antigenic evolution map of human influenza A/H3N2 viruses in Shanghai area over the years was constructed. The results showed that the characteristics of antigenic evolution and genetic evolution were generally similar.Antigenic evolution map and genetic evolution map of human influenza A/H1N1 viruses in the world over the years were constructed. The results showed that there exist some regularity in the evolution and some strains were interspersed. The results also showed the genetic evolution was continuous and the antigenic evolution was puctuated. The mutation at the amino acid position 54,127,193 may be responsiable for the antigenic gap.2. Statistical models for predicting antigentic variants of human influenza A/H1N1 viruses were studied. SVM-RFE(linear), SVM-RFE(RBF), Random forest were used for variable selection. SVM, Random forest, RidgePLS were used as prediction models. Agreement rate, sensitivity, specificity were calculated for evaluating the qualitative performance of the models. The results showed that Random forest was the best model for predicting antigentic variants of human influenza A/H1N1 viruses. The number of variables for prediction models was chosen, which is 30. The agreement rate for SVM-RFE(linear)/RF, SVM-RFE(RBF)/RF, RF/RF were 88.05%,88.05%,87.66%.Therefore,23 positions (position 36,43,54,69,71,73,80,96,121,125,127, 128,140,165,169,189,192,193,204,251,270,271 and 282) were identified as potential immunodominant positions of human influenza A/H1N1 viruses.3. Comparative study on genetic evolution of hemagglutinin between novel influenza A (H1N1) virus and influenza A virus subtype H1 from China. The results showed that there were distant evolutionary relationships between novel influenza A (H1N1) virus HA gene and human influenza A virus subtype H1 HA gene from China, influenza vaccine. At the gene level in China population immunity and vaccine might not provide protection against novel influenza A (H1N1) virus. There was still a little evolutionary distance between novel influenza A (H1N1) virus HA gene and swine influenza A virus subtype H1 HA gene from China. There was no evidence that novel influenza A (H1N1) virus might originate in China.While carrying out the above work, antigenic and genetic evolution of human influenza A/H1N1 and A/H3N2 viruses in Shanghai area in recent years were intuitively understood. The genetic evolution and antigenic variation rule of influenza A viruses were explored. Valuable clues were provided for the prevention and control of influenza. Meanwhile, identifying potential immunodominant positions can assist the annual selection of influenza vaccine strains. The prediction models for antigentic variants of human influenza A/H1N1 viruses may further improve the selection of vaccine strains.