What preserved human tissue from World War I reveals about 1918 flu pandemic

Researchers were able to decipher changes to the virus that happened between the first and second waves of the epidemic over 100 years ago

May 23, 2021 by Sandipan Talukdar

The influenza pandemic during 1918-1919 was the most severe pandemic in the previous century. It is estimated that about one-third of the world’s population was infected with the H1N1 virus which caused the pandemic. The H1N1 virus is thought to have an avian origin.

Sequencing of the virus genome on a large scale was not possible back then due to the absence of required technology which is available today. However, some of the tissue samples had been preserved and other archived tissue sources also exist.

Now, a team of researchers led by evolutionary biologist Sebastian Calvignac-Spencer of the Robert Koch Institute, Berlin, Germany, has been able to sequence large parts of the virus. They collected formalin-preserved lung tissues from the Berlin Museum of Medical History and a collection in Vienna and managed to sequence the genome of the flu virus. The flu virus, like the novel coronavirus, also has RNA as its genetic material. In their study, they sequenced the flu genome from two soldiers (in the Berlin Museum) and from a woman who died in Munich after suffering from the flu.

The team sequenced large parts of the flu genome from the lung samples of two soldiers who died in Berlin in 1918 and also managed to sequence the entire genome of the virus from a woman who died at the same time. The findings of the research have been published in the pre-print repository bioRxiv recently.

There was little research based on extracting the genome of the virus and sequencing it before this. In 2005, US scientists could find the sequence of the genome taken from frozen buried samples in Alaska. Again, in 2013, they reported the sequence of a second genome from a sample preserved in formalin in the Armed Forces Institute of Pathology. The sample was from an autopsy tissue of a flu fatality case in the US.

The researchers who took part in the recent study found that the genome of the virus found from the woman was between 60% and 90% similar to that which was found in the two soldiers. In this kind of study, where the genetic material of a virus is found in archived tissue samples, the researchers do not find the whole genome in almost all the cases. They may find some stretches of the genome. However, those bits can be stitched together to provide an estimate of the entire genome, a tough task to accomplish.

The researchers say that the genomes from the two soldiers were from the first wave of the pandemic, which was comparatively milder than the second wave. The scientists speculate that the virus could have better adapted to humans between the two waves. One way of the adaptation on the part of the virus could be a mutation in a particular protein called the haemagglutinin.

Mutation in a protein means a change in the amino acids. The amino acids are the building blocks of a protein. The haemagglutinin is an important protein of the virus and a mutation of this protein that changes the amino acid glycine to the amino acid aspartic acid could have provided the virus with better adaptation. Glycine is more often found in bird flu viruses whereas aspartic acid is more common in human viruses. Both the genomes of the virus from the two soldiers had aspartic acid.

The researchers could also find evolutionary clues in another protein, called the nucleoprotein. This protein is a structural protein and it helps in determining what species the virus can infect. Sequence from the soldiers, as well as from the woman, all in Germany, carried versions of the nucleoprotein that were more bird-like.

In previously published reports it was found that the nucleoprotein of the virus that carried two mutations was found to have better evasion from the innate antiviral defense produced by the human body. The viral strains that the reports included were from later period of the pandemic.

Again, viral genome from the woman offered other clues to the researchers. The researchers could restore the polymerase complex of the virus from the RNA genome. The polymerase complex is a set of three proteins that together are used in copying the viral genome. They found that the complex from the woman virus was half active in comparison to the polymerase complex from the viral strain found in the samples collected from Alaska (in the US study).

What the German study could reveal so far is that the viral samples were most probably from the first wave of the pandemic based on the genetic information obtained from the genome sequences.

These studies also hint at the possibility of accruing more information about the 1918 pandemic with the help of pathological archives, which are treasure troves for scientists.