Influenza Virus' Genetic Diversity Drives Severity

Researchers at Hong Kong University (HKU) and the Wellcome Trust Sanger Institute have identified a link between the influenza A viruses’ genetic diversity and severity of the infection.

Typically viruses depend on their own RNA polymerase for replication. As a result, the viruses’ descendants have small and random genetic variation. To survive attack from their hosts’ immune systems, the viruses are believed to use these variations to their advantage, according to an HKU statement.

According to study results published in Nature Communications, the investigators passaged an H3N2 influenza virus in the presence of ribavirin, thus inducing mutations and increasing their diversity.

“Applying a fidelity variant with reduced mutational frequency, we provide direct experimental evidence for the role of genetic diversity in IAV pathogenesis,” the investigators wrote.

In creating a sole PB1-V43I mutation, the authors found an increase in viral RNA polymerase fidelity among both seasonal H3N2 and highly contagious H5N1 influenza viruses. Furthermore the researchers witnessed a significant amount of H5N1 viruses with increased RNA polymerase variations present in their mouse models’ lungs. Conversely, the authors also reported “a decrease in viral population diversity at day 3 post inoculation associated with a tenfold reduced lethality and neurotropism in mice.”

Study author Malik Peiris of the Li Ka Shing Faculty of Medicine at HKU touted their discovery, claiming their research provided more insight into a virus’ pathogenic mechanisms.

“A single mutation in one of the influenza polymerase genes (PB1) can lead to decreased genetic diversity and populations of such viruses have reduced disease severity even though they appear genetically identical in all other respects when using conventional genetic sequencing methods,” Peiris explained in a news release that accompanied publication of the study results. “This information provides a target for future development of antiviral drugs and an approach to improve live attenuated influenza vaccines.”