The preserved lung of an 18-year-old Swiss man was used to create the full genome of the “Spanish flu” from 1918, the first complete flu a genome with a precise date from Europe. It offers new insights into the deadly pandemic that claimed the lives of a maximum of 100 million people.
An international research team led by the University of Basel has applied advanced technology to extract traces of the virus from the formaline-conserved organ that was taken from the man who died of serious pneumonia in the cantonal hospital (now university hospital) in Zurich. The teenager’s lung had been held in a university medical collection during the first wave of the pandemic since his death in July 1918.
“This is the first time we have had access to a flu genome of the pandemic from 1918 to 1920 in Switzerland,” said Verena Schünemann, a paleogeneticist and professor of archaeological science at the University of Basel. “It opens new insights into the dynamics of how the virus adapted at the start of the pandemic in Europe.”
With the help of a new RNA sequencing protocol that is designed to extract genetic data from demolished, chemically fixed tissue and comparing the completed genome with that from Germany and North America, the team was able to demonstrate that this voltage of the virus already had three important adjustments. These made it more deadly for people – and they would stay in the virus makeup until the end of the pandemic.
Two of the mutations helped to avoid the virus an important part of the human immune system that is known as MXA, an antiviral protein that normally blocks the flu of replication. This protein is especially important when defending against bird-origin influenza viruses, so these changes made it easier for the virus to spread between people.
The third mutation changed the shape of a surface protein called hemagglutinine, which uses the virus to attach itself and to enter human cells. This made the virus better in recognizing and binding human-specific cell receptors, which increases infection efficiency.
Earlier it was thought that these mutations will later arise in the pandemic – so their presence in the first wave of Switzerland in the spring of 1918 suggests that the virus had evolved quickly and widespread, even before the second and most deadly wave of the pandemic in the fall.
Interestingly, the Zurich virus also showed an unusual genetic diversity in its polymerase (PB2) segment, which suggests a strong natural selection or mixing between viral strains. In comparison with, for example, the H1N1 virus of 2009, the BUG from 1918 had linked a higher variability in important genes to replication and host adjustment. It also shows how quickly influenza viruses can adapt to binding to receptors in people and designing immune system design.
It is not surprising that these rapid adjustments were also a characteristic of the coronavirus in the middle of our most recent pandemic.
One of the most exciting parts of the study is the process with which the team could build this historical genome. Until now, this kind of wet copy had been stored in formalin as unsuitable for RNA analysis. But the extensive genetic data that the researchers could extract from the lung tissue opens the door for unlocking the DNA secrets that are held in thousands of pots in medical and zoological collections around the world.
“Old RNA is only kept for long periods under very specific circumstances,” said Christian Urban, the first author of the study. “That is why we have developed a new method to improve our ability to restore old RNA fragments from such specimens.”
The research-based method of the researchers can capture shorter genetic fragments and also retains RNA strenged orientation. And by discovering the kind of adjustments that is seen in viruses central in earlier pandemies, researchers can get valuable evolutionary instructions that can better prepare us in tackling future outbreaks. Seeing how viruses overflows from animals to people will also be the key in developing vaccine goals.
“A better understanding of the dynamics of how viruses adapt to people for a long period of time, enables us to develop models for future pandemies,” said Schünemann.
The study was published in the magazine BMC Biology.
Source: University of Basel
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