Swiss researchers have successfully sequenced the complete genome of an early 1918 Spanish flu virus strain, a significant milestone that challenges previous understandings of the pandemic's progression. The breakthrough, achieved using an innovative technique on a preserved lung sample from an 18-year-old who died in Zurich in July 1918, indicates that the virus had already acquired crucial mutations for human adaptation and increased virulence early in the pandemic.
The Spanish flu pandemic, which spanned from 1918 to 1920, was a devastating global event, causing an estimated 50 to 100 million deaths worldwide. Uniquely, it disproportionately affected young, healthy adults, often leading to rapid respiratory failure. The fragility of the virus's RNA genome and the limitations of traditional preservation methods had previously hampered detailed study. However, a team led by Verena Schünemann developed a novel protocol for sequencing degraded RNA, enabling the analysis of this first-wave strain's complete genome.
Analysis of the Zurich sample revealed that critical mutations were present by July 1918, earlier than previously believed. These mutations included alterations that allowed the virus to evade the human antiviral protein MxA, a natural defense against avian viruses, and a change in the hemagglutinin protein that facilitated entry into human cells, a mechanism also observed in SARS-CoV-2. These early adaptations likely provided the virus with a significant evolutionary advantage, contributing to its rapid spread and virulence.
This research reshapes the understanding of pandemic virus evolution, suggesting that key adaptations can emerge very early, predetermining a virus's impact. The findings imply that future pandemics could become dangerous long before their widespread effects are apparent. The study, published in BMC Biology, also highlights the potential of well-preserved historical samples, when analyzed with advanced sequencing techniques, to unlock secrets about ancient pathogens.
By studying how the 1918 virus adapted to humans in its initial weeks, researchers aim to better predict the evolution of future pandemic-potential viruses. Rapid identification of such mutations could help anticipate virulence peaks and refine public health strategies. Verena Schünemann stated that reconstructing the 1918 viral genome in Switzerland "opens new perspectives on the virus's adaptation dynamics in Europe at the beginning of the pandemic," underscoring the value of archaeogenetic research in addressing contemporary public health challenges.