Researchers have discovered a unique replication process that allows the flu to evolve to produce enough mutations for the virus to spread and adapt to its host environment, but not so many that unwanted genomic mutations lead to the flu’s demise (catastrophic mutagenesis). The findings, published in the journal PLoS One, overturn long-held assumptions about how the virus evolves.
Understanding how the flu virus replicates and evolves to infect new hosts will help researchers find new ways to fight the virus. Potential therapies could take advantage of these findings by promoting mutagenesis—treatments designed to generate increased mutations that will ultimately kill the virus.
“These new findings give us insights into how we may be able to control viral evolution,” said Baek Kim, PhD, a professor in the microbiology and immunology department at the University of Rochester Medical Center and lead study author. “This research presents an attractive strategy for tackling the flu—making the influenza virus kill itself by amplifying the number of mutations made beyond the desired level, which is lethal for the virus.”
This study disproves the widely accepted idea that the flu virus evolves so efficiently due to its error-prone replication process. The virus requires a high number of genomic mutations to jump from one species to another, such as from a pig to a human, and up until this point researchers believed the error-prone replication process facilitated the mutations needed for the flu to spread. These researchers instead found that the flu’s replication process is not prone to errors; rather, the virus goes through multiple rounds of RNA genome replication in each viral infection cycle, allowing it to produce more than enough genomic mutations necessary for viral evolution and host adaptation.
The flu’s accurate replication process also keeps the virus in check. Given the flu’s multiple rounds of RNA replication per infection, too many mutations would result if the process was highly prone to error, leading to catastrophic mutagenesis.