Genetic sequencing of deadly 1918 influenza virus shows link to bird flu

Lead author holds an affiliate appointment in VCU Department of Anatomy and Neurobiology

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Researchers using the power of genetic sequencing have reconstructed the 1918 influenza virus that killed an estimated 50 million people worldwide and have found that the virus was derived from a bird flu that directly infected humans.

The findings may help scientists pinpoint exactly which genetic changes allowed the bird virus to jump to humans, enable them to recognize other bird viruses that could trigger a pandemic, and aid in the development of effective drugs and vaccines.

Jeffery Taubenberger, M.D., Ph.D., is the lead author of the study with the Armed Forces Institute of Pathology in Washington, D.C. He also holds an affiliate appointment in the Virginia Commonwealth University Department of Anatomy and Neurobiology. He and his colleagues analyzed the genetic sequence of the 1918 human influenza virus and identified a small number of genetic mutations that may explain why the virus is so lethal. In addition, a second group of researchers has used the genetic sequence to recreate the virus and studied its effects in mice. Findings from both studies were published in the Oct. 6 issue of Nature and Science.

“The full sequence is strong evidence that the 1918 flu virus is derived wholly from an ancestor that originally infected birds,” Taubenberger said in the article. A recent New York Times article reported that bird flu viruses called H5N1 are emerging in Asia, generating concern that a transformation in one of the current bird flu strains could make it infectious in humans.

Taubenberger and colleagues have been working to unravel the genome sequence of the 1918 virus for nearly a decade. In this most recent work, the final three genes that make up half of the virus’ length were identified. Previously, they had published the sequences of five of the eight genes that make up the virus.

The team retrieved tiny fragments of 1918 viral genes from snippets of lung tissue from two soldiers and an Alaskan woman who died in the 1918 pandemic. They traced the genetic sequence of the 1918 virus and used tools of molecular biology to synthesize it. At a secure laboratory facility at the Centers for Disease Control and Prevention, they infected mice and human lung cells with the virus.

Researchers observed that the 1918 virus acts much differently from normal human flu viruses by infecting cells deep in the lungs of mice. Furthermore, the 1918 virus infects lung cells that normally would be impervious to flu, and unlike other human flu viruses, this one kills mice.

According to the article in Nature, researchers have already identified 25 changes in the protein sequences of the 1918 strain that have been present in subsequent human flu viruses. Taubenberger said these mutations are likely to be particularly important.

While this new work holds great importance – leading the way for investigators to identify dangerous viruses before it’s too late and offering ways to disable them – the dangers of resurrecting the virus, and the possibility that the recreated strain could be accidentally released, or even deliberately released as a bioweapons agent, has raised some concern in the scientific community.

“We are aware that all technological advances could be misused. But what we are trying to understand is what happened in nature and how to prevent another pandemic. In this case, nature is the bioterrorist,” said Taubenberger.

Taubenberger earned both his medical and post-doctorate degrees from the VCU School of Medicine and was named Medicine's Alumni Star in 1999, approximately four years after his work with the bird flu virus began.

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