The "Spanish Flu" pandemic of 1918-1919 was one of the deadliest plagues in human history, killing as many as 50 million people. Now researchers have used genetic sequencing to bring the virus back to life and have uncovered new clues to what made it so virulent.
The findings grow out of a decade-long effort by Armed Forces Institute of Pathology pathologist Jeffrey Taubenberger. Since 1995, Taubenberger's group has been piecing together the sequence of the virus' eight genes using tissue from a victim found in permafrost in Alaska (ScienceNOW, 6 February 2004). This week in Nature, the team reports the sequence of the final three genes, which together encode the machinery required for virus replication.
Once the full sequence was in hand, other researchers set about reconstructing the 1918 virus. Virologist Peter Palese's team at the Mount Sinai School of Medicine in New York City stitched the eight genes into a regular flu virus genome and shipped the DNA to the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia. There, virologist Terrence Tumpey inserted the DNA into cells to make live virus.
The resurrected virus apparently hasn't lost any of its kick. It killed mice in 3 to 5 days and caused severe lung inflammation reminiscent of that reported by doctors who examined 1918 flu victims, Tumpey, Taubenberger, Palese, and others report 7 October in Science. The virus also killed chicken embryos, unlike most human flu viruses.
A closer examination of the virus revealed some other surprises. It can apparently infect many kinds of cells beside lung cells because it doesn't rely on an enzyme that is only present in specific cell types. In addition, some of the 1918 flu's genes appear to allow it to replicate very efficiently in human bronchial cells. Because these genes are similar to those found in bird flu, the 1918 flu likely arose from a bird virus. Moreover the close resemblance means it did not need to mix its genes with a human influenza virus to infect people, as did two more recent pandemic flu viruses. Instead, the virus likely jumped straight to humans and began killing them, Taubenberger notes. Some isolates of the H5N1 avian influenza virus now in Asia also share these mutations, which could help explain why H5N1 has managed to infect and kill about 60 people.
Recreating the 1918 strain "had to be done, and it's produced some extremely interesting results," says flu researcher Robert Webster of St. Jude Children's Research Hospital in Memphis, Tennessee. Tumpey's team hopes its work will lead to better antiviral drugs and vaccines for heading off the next influenza pandemic.