Correlation of polymerase replication fidelity with genetic evolution of influenza A/Fujian/411/02(H3N2) viruses.

ABSTRACT

Influenza virus evolves continuously through mutations presumed to result from evolutionary pressure driving viral replication. This study examined the relationship between the genetic evolution and replication fidelity of influenza viruses. Analysis of influenza sequences from National Centre for Biotechnology Information (NCBI) database revealed a gradual decrease in the rate of genetic evolution of A/Fujian/411/02(H3N2)-like variants after the emergence and predominance of the A/H3N2 Fujian strain in 2002. This decrease may be related to an increase in replication fidelity, which was investigated by assessing mutation frequencies of reassortant viruses carrying the PB1 segment of Fujian variants isolated between 2003 and 2005 in a sequencing-based plaque assay. The data revealed a threefold decrease in substitution per site of the reassortant viruses carrying the Fujian PB1 segments isolated in 2004-2005 compared with those circulating in 2003. The decrease in mutation frequency paralleled a decrease in genetic evolution of the Fujian variants from the NCBI database. This correlation implicates changes in the polymerase replication fidelity as contributing to altered genetic evolution of influenza viruses.