Influenza A Model Receives a Face-Lift

The current model of the influenza A virus just got a face-lift, and the results have revealed new information that may help public health agencies develop more targeted vaccines against the virus in the future. The researchers who remodeled the influenza virus are from the University of Pittsburgh Schools of the Health Sciences. Their findings will be published in an upcoming issue of Nucleic Acids Research.

According to the research, instead of double-stranded DNA, the influenza A virus uses “8, negative-sense, single-stranded RNA segments that are named according to the primarily encoded protein: PB2, PB1, PA, HA, NP (nucleoprotein), NA, M and NS (listed from longest to shortest segment). The segments range in size from ∼0.9 to 2.3 kb with a total genome size of approximately 13.5 kb. All 8 RNA segments must come together inside a virus particle to be fully infectious.”

The classic 1970’s model of the influenza virus shows that the proteins coat the RNA, “like beads, evenly spaced along a string.” But, senior authors on the study, researchers Seema S. Lakdawala, PhD, assistant professor in Pitt's Department of Microbiology & Molecular Genetics, and Nara Lee, PhD, assistant professor in Pitt's Department of Microbiology & Molecular Genetics, who specializes in RNA interactions, wanted to know if there may be any “areas along the influenza RNA strand that are more open, and, therefore, more able to associate with other RNA segments in order to arrive at a package of all 8 segments.”

By using “a process called high-throughput sequencing of RNA by crosslinking immunoprecipitation (HITS-CLIP) on 2 strains of influenza A, including the 2009 H1N1 pandemic strain, to get a better understanding for where the proteins bind to the RNA and to see if there were any areas of naked RNA,” the researchers found that there are, in fact, loopholes (exposed RNA loops) between the beads. It is these loopholes that the virus uses to “swap genetic material and give rise to new strains of flu,” according to a press release on the research. Learning more about these loopholes may be the key to fighting the virus and predicting future flu pandemics.

Dr. Lakdawala spoke about the results of their findings in the press release, stating, “Although influenza has plagued humankind for hundreds of years and poses a substantial public health threat every winter, we know surprisingly little about flu pandemics. Our discovery may give insight into how the flu virus continually evolves, opening the door to better vaccines and antivirals.”

To this end, “the team is pursuing several potential research opportunities, including predicting the ways different viruses could share genetic material to make new viruses,” according to the press release.

Dr. Lakdawala added, “It's really exciting to suddenly have all these research possibilities open up based on this one discovery. The reason no one's uncovered this yet is because we all took for granted that 50-year-old research on the genome architecture, which looked really nice and had an easy explanation, was the full story. It shows that if we don't constantly resample and question scientific dogma, we could miss a big opportunity."