Study for the correlation between genetic diversity and antigenic variation of hemagglutinin in influenza A viruses

Abstract

Objective To study the correlation between genetic diversity and antigenic variation of hemagglutinin in influenza A viruses and analyze the coincidence of these two variations with epidemiological data. MethodsA/H1N1 and A/H3N2 influenza viruses isolated from flu-like cases in Shanghai and surrounding areas during 2005-2007 influenza seasons as well as some vaccine strains for northern hemisphere recommended by WHO were used. The correlation between genetic diversity and antigenic variation of hemagglutinin in influenza A viruses was studied. Full-length sequence encoding hemagglutinin was determined and analyzed by phylogenetic tree analysis. Golden hamsters were immunized with inactivated influenza viruses, and their sera were titrated for the virus hemagglutinin by hemagg/utination inhibition assay (HIA). HIA data were clustered and mapped. Results A/H3N2 viruses isolated in Shanghai and WHO recommended vaccine strains, such as A/Sydney/5/97-like and A/Fujian/411/2002-like, were located at different clusters. The distance was associated with time when the virus was isolated. The more the interval time between isolations, the longer was the distance. Similar trend was found in antigenic variation. In A/H1N1 strains, however, the antigenic variation was not in accordance with the genetic diversity. The distances of genetic diversity between Shanghai isolates and the WHO recommended vaccine strain, A/New Caledonla/20/1999-like, were influenced by time. Whereas, the distance of antigenic variation was not only associated with the time of isolation but also with the virus strains isolated from sporadic or clustered cases. Conclusions The genetic diversity of hemagglutinin is similar to antigenic variation of hemagglutinin in influenza A viruses, and the mutation and evolution of hemagglutinin antigen can be better reflected with HIA by using the immune sera of epidemic strains. Key words: Influenza A virus; Genetic diversity; Antigenic variation; Cluster analysis