A recent discovery made by researchers from the University of Pittsburgh (Pitt) Schools of the Health Sciences revealed a loophole in which the influenza virus packages its genetic material to give rise to new strains of the flu.
The research, detailed in a recent issue of the journal Nucleic Acids Research, showed how one strain of influenza interacts with another strain inside a cell, allowing the strains to swap genetic material with one another to develop an entirely new influenza strain.
According to the World Health Organization (WHO), the highly infectious disease and its associated strains cause approximately 375,000 deaths per year worldwide. Typical symptoms of infection include high fever, muscle pains, headache, lethargy, and nausea. More severely, the virus can lead to complications such as viral pneumonia, sinus infections, and the worsening of conditions such as asthma.
“Although influenza has plagued mankind for hundreds of years and poses a substantial public health threat every winter, we know surprisingly little about flu pandemics,” Seema S. Lakdawala, assistant professor of microbiology and molecular genetics at Pitt, said. “Our discovery may give insight into how the flu virus continually evolves, opening the door to better vaccines and antivirals.”
The influenza virus is comprised of eight RNA segments bound by a protective nucleoprotein. Instead of using double-stranded DNA, influenza uses a single-stranded RNA to replicate. In order for the virus to become infectious, all eight RNA segments must come together inside a virus particle.
In the traditional model of influenza, originally developed in the 1970’s, nucleoproteins coat RNA like evenly-spaced beads along a string. However, the dated technology used to develop the original model left out some of the unique aspects of the virus, such as exposed RNA loops.
Lakdawala, along with Pitt assistant professor of microbiology and molecular genetics Nara Lee, worked in tandem to research if there were areas along influenza RNA strands that are more adept to associate with other RNA segments. In order to understand where proteins bind to RNA, the two researchers utilized a process called high-throughput sequencing of RNA by cross-linking immunoprecipitation on two strains of influenza A.
“Honestly, we didn’t expect to find any since we had all learned the ‘beads on a string’ depiction of viral RNA,” Lakdawala said. “But, amazingly, there are several stretches where the RNA was not bound by the nucleoprotein. This discovery opens up a whole new area of research.”
The team found that there were areas of RNA rich with protein coating while others were more susceptible to binding to other viral RNA during reassortment.
In a release, the Pitt researchers said they will soon be potential research opportunities, including how to predict the ways different influenza viruses could share genetic material to create new viruses, which could point global scientists to specific reassortment most likely to spark a flu pandemic.
Funding for the study was provided by the University of Pittsburgh and the National Institutes of Health (NIH).