Study For The Correlation Between Seasonality And Genetic Diversity In Influenza A Virus From Shanghai

Influenza is one of the most important respiratory infections threatened the human health for a long time, epidemic or pandemic of influenza is based on antigenic drift and antigenic shift resulted from genetic diversity and reassortment. Despite the recent study for genetic diversity, many aspects of the evolutionary and epidemiological dynamics of influenza A virus remained opaque. In particular, there had been no rigorous measurement of viral diversity across time and among subtypes. The clock-like consistency of the winter incidence peaks of influenza virus represented one of the strongest examples of seasonality in infectious disease. However, the reasons that human influenza epidemics arise and then peak at winter in temperate regions of the northern hemispheres were unknown. Various theories had been proposed to explain which factor could help to shape influenza seasonality that remain largely untested and there was lack of study concern about correlation between genetic diversity and seasonality in influenza A. To help to resolve these issues, we quantify diversity of influenza A virus across time and among subtypes to explore the correlation using reasonable epidemiological methods and bioinformatics methods, it including five main contents as follow.1. Appropriate surveillance spot and website were founded in Shanghai area to collect influenza-like cases report in long period. The seasonal epidemic peak of influenza incident was analyzed by using time-series analysis method. It was revealed that there were 2 seasonal peaks of influenza-like cases in Shanghai with a consistent 6-month interval. It was different from the peek of influenza-like cases in northern China which only had one winter peak with 12-month interval.2. A/H3N2 and A/H1N1 isolations sampled from surveillance system and that was illustrative of large populations in Shanghai regions were selected and complete genome sequence was detected for the Hemagglutinin (HA), Neuraminidase (NA) and basic polymerase 2 (PB2) gene. The genetic diversity across time and among subtypes of three main segments was measured by employing Bayesian MCMC analyses. The evolutionary dynamics of influenza A virus main 3 segment was investigated comprehensively combined with concern epidemiological data. This analysis demonstrated that the genetic diversity for two different subtypes of influenza virus A was variance. In general, evolutionary speed of A/H3N2 was quicker than A/H1N1. The evolutionary speed of HA was faster than other and PB2's was the lowest in same subtype, which was connected with the adaptive diversity of influenza A virus for escaping host's immunity. The absolute amount of genetic diversity of A/H3N2 was higher than A/H1N1 in most study period. The amount of A/H1N1 was less 1/3 than the amount of A/H3N2 even though in its epidemiological dominant. This result demonstrated that A/H1N1 genetic diverse was more stable than A/H3N2 so it could not breakthrough human immunity shield and the pressure from A/H3N2. The high absolute amount of genetic diversity did not indicate that the improvement of transmission ability, which should combine the data of theory infection population result in genetic diversity and comprehensively assessment and then could get the more accurate conclusion.3. Typical influenza A virus was selected to find out resistant variant for oseltamivir carboxylate known as an effective drug to influenza. It could be indirectly demonstrated that genetic diversity had induced key point antigenic diversity. The result indicated that genetic diversity did not result in essential antigenic change, point mutation and adaptive diversity were key characters in genetic diversity.4. Sera from poultry associate workers were selected and examined to explore the potential infectious path from non-human host influenza A virus to human and investigate sensitivity of human infected non-human host influenza A virus. It was demonstrated that people in study area were all sensitive to non-human host influenza A virus. Hemagglutinin inhibitor antibody against poultry influenza virus subtype H9 had been found in poultry exposure and non-poultry exposure population. The antibody positive rate was 17.9% in poultry exposure worker and 2.6% in non-poultry exposure population. Comparing with non-exposure population, poultry exposure population had an adjusted odds ration (OR) of 3.392. The distribution of hemagglutinin inhibitor titer against influenza A virus subtypes H1N1 and H3N2 was no different between two groups, but hemagglutinin inhibitor titer was high within two population. If the seasonal influenza vaccine did not taken, especially for subtype H3N2 that had higher absolute amount genetic diversity, the antibody positive rate was a 30%.5. In this study, we explored the correlation between seasonality and genetic diversity in influenza A virus and gained some knowledge for the influenza prevention and control. The genetic diversity of influenza A virus had only one visible peak appeared in each winter. It was different from influenza-like case that had two peaks and its winter-spring peak went through calendar year. These results showed that influenza A virus adaptive diversity was forced under the host immunity pressure and induced a new epidemic.Our study suggested that there was seasonal epidemic of influenza incident in Shanghai area, stochastic point mutation and adaptive diversity were key determinants of short-term evolution in influenza A virus, there were not manifest phenotype change that resulted in drug-resistant strain. Seasonality of influenza A virus was mainly influenced by adaptive diversity under the circumstances that climate didn't change frequently, population generally sensitive to influenza virus and its composition, life style and immunity level basically retained stable, etc.