Study uncovers a lethal secret of 1918 influenza virus

By infecting monkeys with the virus, the team was able to show that the 1918 virus prompted a deadly respiratory infection that echoed historical accounts of how the disease claimed its victims.

Importantly, the new work shows that infection with the virus prompted an immune response that seems to derail the body's typical reaction to viral infection and instead unleashes an attack by the immune system on the lungs. As immune cells attack the respiratory system, the lungs fill with fluid and victims, in essence, drown. The mechanisms that contribute to the lethality of the virus were uncovered by University of Washington researchers using functional genomics, a technique in which researchers analyze the gene functions and interactions. Learning more about the virulence mechanisms of the 1918 flu virus may help researchers understand how to keep the virus from causing such a severe immune response.

"This study in macaques, combined with our earlier research showing the host response in mice infected with the 1918 flu, suggests that the host immune response is out of control in animals infected with the virus," said Michael G. Katze, professor of microbiology at the University of Washington in Seattle, who led the functional genomics portion of the new study and led the previous mouse-based study. "Our analysis revealed potential mechanisms of virulence, which we hope will help us develop novel antiviral strategies to both outwit the virus and moderate the host immune response."

The same excessive immune reaction is characteristic of the deadly complications of H5N1 avian influenza, the strain of bird flu present in Asia and which has claimed nearly 150 human lives but has not yet shown a capacity to spread easily among people.

"What we see with the 1918 virus in infected monkeys is also what we see with H5N1 viruses," Kawaoka says, suggesting that the ability to modulate immune response may be a shared feature of the most virulent influenza viruses.