Evidence of an absence: the genetic origins of the 1918 pandemic influenza virus

Abstract

Annual outbreaks of influenza A infection are an ongoing public health threat and novel influenza strains can periodically emerge to which humans have little immunity, resulting in devastating pandemics. The 1918 pandemic killed at least 40 million people worldwide and pandemics in 1957 and 1968 caused hundreds of thousands of deaths. The influenza A virus is capable of enormous genetic variation, both by continuous, gradual mutation and by reassortment of genome segments between viruses. Both the 1957 and 1968 pandemic strains are thought to have originated as reassortants in which one or both human-adapted viral surface proteins were replaced by proteins from avian influenza strains. Analyses of the genes of the 1918 pandemic virus, however, indicate that this strain might have had a different origin. The haemagglutinin and nucleoprotein genome segments in particular are unlikely to have come directly from an avian source that is similar to those that are currently being sequenced. Determining whether a pandemic influenza virus can emerge by different mechanisms will affect the scope and focus of surveillance and prevention efforts.

Figure 1. Comparison of the nucleoprotein (NP) genome segment from the 1918 pandemic influenza virus and two avian strains with the overall avian consensus sequence.

The data show that although the amino acid sequence of the 1918 NP is similar to the overall avian consensus at the amino acid level, it is highly divergent at the nucleotide level.

Figure 2. Comparison of the haemagglutinin 1 (HA1) domain from the 1918, 1957 and 1968 pandemic viruses and various other avian strains with their avian consensus sequence.

The data show that the HA of the 1918 pandemic virus differs from the H1 avian consensus to a much greater extent than the 1957 human H2 and 1968 human H3 differ from their respective avian consensus sequences.