Just in time for flu season comes the discovery that a single protein may largely explain the unprecedented deadliness of the 1918 influenza epidemic. The finding should help infectious disease experts spot future flu viruses that pose the most risk of causing another global pandemic.
The 1918 outbreak--also known as the Spanish flu--was the deadliest strain of flu virus the world has ever seen (ScienceNOW, 17 January). Estimates of fatalities range from 40 million to 100 million. Some people fell victim to the flu virus itself, but many of the deaths were due to the pneumonia that people developed as a result of damage to their lungs. Why was the virus so deadly? Scientists suspect that a recently discovered protein called PB1-F2, which is found in many flu viruses, including the H5N1 bird flu strain that has killed 202 people, may hold some answers.
To get a better handle on the role of PB1-F2 in the 1918 epidemic, a team led by Jonathan McCullers, a virologist at St. Jude Children's Research Hospital in Memphis, Tennessee, genetically modified a mouse strain of flu virus to produce a PB1-F2 protein identical to that in the 1918 strain. When the researchers dripped high doses of the modified virus into the noses of mice, all of the animals died within 8 days and had more lung inflammation than animals receiving similar doses of the same flu virus with unaltered PB1-F2.
In a separate experiment, the researchers gave mice nonlethal doses of the modified flu virus and then infected them with the pneumonia-causing bacterium, Streptococcus pneumoniae. All of the animals died within 4 days and showed evidence of severe pneumonia, the team reports in the October issue of Cell Host & Microbe. In contrast, 80% of the mice that received the unmodified virus were alive 4 days after exposure to the pneumonia bacterium and 20% were still alive when the study ended at 14 days.
"This is one of the big reasons 1918 was so bad, because PB1-F2 allowed bacteria to cause more problems due to lung inflammation and damage," McCullers says. How PB1-F2 amplifies flu virulence remains uncertain, but he says the protein could be a potential target for flu drugs, with the goal being to suppress it to help reduce lung damage and subsequent pneumonia.
Terrence Tumpey, a microbiologist with the Centers for Disease Control and Prevention in Atlanta, Georgia, says monitoring the PB1-F2 protein in flu viruses could help determine which ones pose the most threat to public health. "It could help us recognize if a particular virus is something we have to watch out for," Tumpey says.