Influence of genetic reassortment on the progeny virus production of a novel influenza virus *
Influenza A viruses are widely distributed among birds and mammals. Influenza viral antigenicity is determined from 2 kinds of spike proteins, hemagglutinin（HA） and neuraminidase（NA）, for which there are many antigenic varieties. The viral genome is composed of 8 segmented RNAs, and when two kinds of viruses simultaneously infect a host cell the reassortment of viral genomic RNAs can easily occur. This produces progeny viruses with new genetic combinations. Thus genetic reassortment is regarded as the most important pathway for the generation of a new pandemic form of an influenza virus. To assess the probability of the generation of new reassortants, we examined the efficiency of the introduction of HA and NA genes from an H3N2 subtype virus into a background of a WSN （H1N1 subtype）virus by reverse genetics. The replacement of HA alone reduced progeny production to approximately 1/10, and the double replacement of HA and NA to approximately 1/100. Electron microscopy revealed that the original WSN had spherical uniform particles, whereas the replacement of HA caused a slight increase in the diameter of viral particles, while the double replacement of HA and NA caused a pleomorphism. These results showed the possibility that the replacement of HA and NA may affect viral morphogenesis and considerably reduce virus production. However, such replacement is essential for the generation of a new pandemic strain. Thus, genetic reassortment is not always an easy way for a new virus to be generated. If such a reassortant could gradually obtain efficient growth characteristics by mutations through repetitive infections and replications, it could finally result in a pandemic strain being produced. However, during the low growth period, reassortant would require some selection pressure, such as circumstances in which the original virus could not grow efficiently, to survive and overcome the original virus. (Accepted on July 31, 2009)
