The 1918 Spanish-influenza outbreak remains the worst pandemic in recorded history, killing more than 20 million people worldwide. With an eye toward preventing similar health disasters, researchers have long speculated about why the 1918 outbreak was so deadly (SN: 9/28/02, p. 196: New Drugs Beat Old Flu: Antiviral agents counter deadly 1918 influenza). Now, findings reported in the Oct. 7 Nature suggest that differences in a single viral gene made the 1918 flu strain particularly virulent.
Using a method called reverse genetics, Yoshihiro Kawaoka of the University of Wisconsin–Madison and the University of Tokyo and his colleagues engineered a relatively mild flu virus to carry two genes from the 1918 strain. In 1990, scientists had sequenced these genes from preserved lung tissue obtained from victims of the 1918 pandemic. The genes code for the proteins hemagglutinin and neuraminidase, which help flu viruses enter and infect cells.
Mice infected with the engineered virus quickly sickened and died. By inoculating mice with engineered viruses that carried just one or the other of the two genes, Kawaoka’s team found that the hemagglutinin gene alone was enough to increase the virus’ pathogenicity.
Within days, mice inoculated with this variety came down with severe and deadly infections. Mice infected with a virus carrying only the neuraminidase gene showed just mild flu symptoms.
Although all flu viruses carry a variant of the hemagglutinin gene, Kawaoka says that the 1918 version “does something different, but we don’t know how it does it.”