Modern Bird Genes Have Potential To Cause A Pandemic Similar To 1918 Spanish Flu
June 12, 2014

Modern Bird Genes Have Potential To Cause A Pandemic Similar To 1918 Spanish Flu

Lawrence LeBlond for - Your Universe Online

Avian bird flu strains that exist today share very similar characteristics with the deadly 1918 Spanish Flu strain that killed nearly five percent of the world’s population. That flu virus pandemic was the worst outbreak ever recorded and new research has found that only a few amino acids separate viral proteins currently found in bird populations from those that existed during the 1918 virus. The new evidence suggests a similar deadly virus may emerge in the near future.

Publishing a paper in the journal Cell Host & Microbe, an international team of researchers searched public databases to identify eight genes from influenza viruses isolated from wild ducks that possess remarkable genetic similarities to the genes that made up the 1918 pandemic flu virus. The Spanish Flu infected some 500 million people around the world, killing an estimated 40 million of them.

Led by Yoshihiro Kawaoka, an international expert on influenza from the University of Wisconsin-Madison, the new work shows “there are gene pools in nature that have the potential to cause a severe pandemic in the future.”

"Because avian influenza viruses in nature require only a few changes to adapt to humans and cause a pandemic, it is important to understand the mechanisms involved in adaptation and identify the key mutations so we can be better prepared," Kawaoka said in a statement. "Research findings like this help us assess the risk of outbreaks and could contribute to routine surveillance of influenza viruses."

To assess the risk posed by a virus that could acquire all eight of the 1918 flu genes, Kawaoka and colleagues used reverse genetics methods to generate a virus that differed from the Spanish Flu virus by only three percent of the amino acids that make the virus proteins. They discovered the resulting virus was more pathogenic in mice and ferrets than a typical avian flu virus, but was not as pathogenic as the 1918 virus and did not transmit via respiratory droplets, the typical mode of flu transmission.

The study group then conducted additional experiments to see just how many changes were needed for the avian 1918-like virus to become transmissible in ferrets. The team identified seven mutations in three viral genes that allowed the pathogen to transmit as freely as the 1918 virus. The resulting virus, comprised of genetic factors found in both wild and domestic birds, shows the genetic ingredients for a potentially deadly flu virus already exist in nature and have the ability to combine to form such a virus, according to Kawaoka.

Kawaoka explained how his team’s work is important because it shows the potential risk that already exists. Knowing what genes to look for, he added, will help predict the likelihood of an emerging strain of pandemic flu and could help scientists better devise strategies to counter a deadly outbreak.

The work also provides critical insight and evidence for the mechanisms responsible for adaptation of avian influenza viruses to mammals. One mutation in the 1918-like avian virus, for example, is responsible for increased virus growth in mammal cells. Mutations in hemagglutinin, a protein found on the surface of influenza viruses that binds to host cells, alter the protein’s stability, which could potentially enhance the virus’s ability to infect the upper respiratory tract of humans.

One of the key findings in the new study is that sera from individuals vaccinated with the current seasonal flu vaccine – which protects against 2009 H1N1 influenza – reacted with the novel transmissible 1918-like avian virus, noted Kawaoka. This suggests protection against a potential pandemic threat exists in the currently available vaccine. As well, the team determined the novel transmissible virus is expected to be sensitive to the antiviral drug oseltamivir.

“Eventually, we hope to be able to reliably identify viruses with significant pandemic potential so we can focus preparedness efforts appropriately,” said Kawaoka.

Kawaoke maintained the study was conducted under specially designed high-containment conditions, utilizing biosafety practices at UW-Madison. The study was reviewed by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health and complied with the United States Government Policy for Oversight of Life Sciences Dual Use Research of Concern.

“The point of the study was to assess the risk of avian viruses currently circulating in nature,” explained Kawaoka.

"The worst-case scenario is the emergence of a novel avian influenza virus that exhibits high pathogenicity in humans, like H5N1 viruses, and efficient transmissibility in humans, like seasonal influenza viruses," Kawaoka said. "Our findings demonstrate the value of continued surveillance of avian influenza viruses and reinforce the need for improved influenza vaccines and antivirals to prepare for such a scenario.

“With each study, we learn more about the key features that enable an avian influenza virus to adapt to mammals and become transmissible,” said Kawaoka. “Eventually, we hope to be able to reliably identify viruses with significant pandemic potential so we can focus preparedness efforts appropriately.”