Genetic analysis: seasonal influenza viruses originated from the 1918 pandemic

The Spanish flu was the deadliest pandemic of the 20th century. In the period between 1918 and 1920, there were three major waves of disease and many casualties. Experts estimate that 50 to 100 million people worldwide have died as a result of a particularly contagious influenza virus.

Today, it is difficult to determine how dangerous influenza viruses evolved during the pandemic at that time and in the period after it. While SARS-CoV-2 has already been sequenced millions of times due to technical possibilities, there are hardly any well-preserved samples of the Spanish flu virus.

Reconstruct another genome

An international research team led by Sebastian Calviniak Spencer of Germany’s Robert Koch Institute has now made a significant contribution to the available data on the Spanish flu. The team took a close look at a total of 13 lung tissue samples from Germany and Austria since the time of the pandemic. They were able to sequence the entire virus genome from a lung preparation from Charité in Berlin, and partially from two other samples.

Navina Wedolin, Berlin

Tissue samples at the Museum of Medical History in the Charité, Berlin

Calviniak Spencer said at a press conference presenting the results of the study with virologist Thorsten Wolff, who is also of Robert Koch who presented the institute.

The examined specimens came from Austria from the pathological anatomical collection of the Vienna Natural History Museum in Narenturm Vienna. However, the team did not find any usable viral genome in it.

The first data from Europe

With what they claim is the first completely reconstructed genome of the Spanish flu from Europe, experts have examined the differences between it and samples collected so far. Most of these are from the United States.

In addition, it is also the first genome of the Spanish flu to come from some time before the first peak of the epidemic at that time. Therefore, the team was able to examine how the deadly virus has changed over the course of the pandemic by comparing it to more recent samples. It has long been assumed that modern H1N1 influenza viruses were at least partially descended from H1N1 at the time.

The researchers are now presenting the results of their investigations in the journal Nature Communications. Due to the very small number of samples worldwide, according to experts, it is a mistake to consider the newly established hypotheses as indisputable. More samples and investigations are needed to verify the results more closely.

Direct descent is possible

Using genetic analysis, the team created a model showing how the Spanish flu might have evolved since the deadly epidemic peaked in 1918. For this purpose, the researchers used a method (a molecular clock) in which they could estimate the point in time at which two types of viruses separated from an ancestor subscriber.

And they found evidence that modern seasonal influenza H1N1 may not only be partial, but entirely derived from the Spanish flu virus. Therefore, all parts of the genome of modern H1N1 influenza viruses can originate from the virus strain at that time. “We therefore contradict previous assumptions that seasonal viruses were created by shuffling different virus genomes,” Calvinac Spencer says.

Mutations protect against the immune response

Before the H1N1 influenza virus became dangerous to humans, it was mainly found in birds. It has not yet been researched how the virus is able to bypass the human immune system and cause so many deaths. However, comparison of samples before the first peak of the epidemic and the genome already present from the time after it provided a possible explanation for this.

In the genome of a virus from the United States, researchers found two mutations in a protein that potentially protects the genome of influenza viruses from the main wave of the human immune system better than the viruses did. Another enzyme responsible for transcribing genetic material was also more active from a sample from Berlin. In the context of the epidemic, the virus has adapted to its new victims and improved its genome to replicate in human cells.

Hardly any predictions are possible

The researchers also found evidence that the Spanish flu was somewhat similar to the current Covid-19 pandemic. Back then, as now, there were waves of illness that culminated in the fall of 1918 with the Spanish flu. DNA sequencing will also show that the Spanish flu spread primarily through local infection, but in some cases the viruses traveled farther.

According to Wolff, it is wrong to compare the frequently ongoing SARS-CoV-2 pandemic to the Spanish flu. He explains: “Coronaviruses and influenza viruses belong to completely different virus families. So they are not related to each other, and therefore they differ in some areas. “It is often the case with coronaviruses that are displaced by infectious viruses of the same family. But in the case of influenza viruses, the researchers were unable to find any evidence of such a process.

Seasonal waves of disease are possible

However, it may be possible to find parallels between the Spanish flu and the coronavirus pandemic in the future. At present, however, data on H1N1 influenza viruses from the 20th century are too few to make guaranteed correct predictions. Preservation and research of specimens that are still present must therefore be improved, according to the researchers.

One thing, based on the study findings, could also apply to the ongoing CoV pandemic: “One could probably assume that coronaviruses will also be with us for a very long time – perhaps seasonally. How long and when will sick seasons last?” explains Wolf. ?

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