The 1918 influenza virus: A killer comes into view.

In the fall and winter of 1918–1919, an influenza pandemic of unprecedented virulence swept the globe leaving 40 million or more dead in its wake. The virus responsible for this catastrophe was not isolated at the time, and it seemed that this very lethal infectious agent was lost for study. However, it has recently become possible to study the genetic features of the 1918 “Spanish” influenza virus using frozen and fixed archival autopsy tissue. Gene sequences of the 1918 virus can be used to frame hypotheses about the origin of the 1918 virus and to look for clues to its virulence. The study of the 1918 virus is not just one of historical curiosity. Since influenza viruses continually evolve by mechanisms of antigenic shift and drift, new influenza strains, as emerging pathogens, continue to threaten human populations. Pandemic influenza A viruses have emerged twice since 1918, in 1957 and 1968. The risk of future influenza pandemics is high. An understanding of the genetic makeup of the most virulent influenza strain in history may facilitate prediction and prevention of such future pandemics. Recent reviews dealing with more historical aspects of the 1918 pandemic are listed under Selected Reading.