H1N1 traced to 1918 pandemic

The virus responsible for the Spanish flu in 1918 created a ‘viral legacy’ that continues to this day, according to a study published recently in the New England Journal of Medicine .

According to the authors of the report, the Spanish flu's H1N1 virus, which caused tens of millions of deaths in 1918, was also transmitted from humans to pigs during the pandemic. Tracing the lineage of the virus in this research shows that it continues to evolve in both humans and pigs 90 years later.

All human-adapted influenza A viruses "are descendants, direct or indirect, of that founding virus" says Jeffrey Taubenberger, a co-author of the report and a senior investigator at the Laboratory of Infectious Diseases of the National Institute of Allergy and Infectious Diseases in the US.

Key points from this research

• All flu viruses contain eight genes in total, including two that contain instructions for producing the proteins hemagglutinin (H) and neuraminidase (N), which allow the virus to attach to a host cell and spread from cell-to-cell.
• There are 16 sub-types of the H protein and nine sub-types of the N protein a flu virus can possess. This offers 144 possible HN combinations, but to date, only three (H1N1, H2N2 and H3N2) have been observed to be fully adapted for infecting humans.
• There are other combinations, such as H5N1, a strain of bird flu virus, but these have only occasionally infected a small number of humans.

Where was the article published?

This article was written by D M Morens and colleagues from the National Institute of Allergy and Infectious Diseases, Bethesda, in the US. It was published in the New England Journal of Medicine. No potential conflicts of interest were reported.

A related article on the evolution of the current pandemic strain of the H1N1 virus was also published in the same issue and has been covered in Behind the Headlines.

What kind of study was this?

This was a review article written by acknowledged experts in the field, explaining the lineage of the pandemic flu virus seen in 1918 and relating it to the emergence of the pandemic H1N1 strain currently circulating.

What do the researchers say?

The researchers explain that descendents of the H1N1 influenza A virus that caused the pandemic of 1918–1919 have persisted in humans for over 90 years, and have continued to contribute their genes to new viruses that have caused epidemics, new pandemics and epizootics (epidemics in animal populations).

The current pandemic strain is thought to originate from two unrelated swine viruses, including a derivative of the 1918 human virus. It also appears to contain genes from human, bird and swine flu viruses. The authors sought to detail the family history or ‘lineage’ of this virus, mapping out the complex relationship between a number of different strains that may have exchanged genetic material.

The authors created an analogy to explain how genetic material transfers and mutates. They said it is helpful to think of influenza viruses as a team of eight genes working together. Occasionally the viruses ‘trade’ one or more team members to make way for new genes, or ‘players’. These new players bring with them ‘unique skills’, and through trading genes in this way (called ‘shift’) and by accumulating mutations (called ‘drift’) the influenza viruses are able to change and evade the immune system.

The authors also researched the mortality rates in seasonal epidemics and previous pandemics, expressing doubt over the claim that gene shift always cause severe pandemics while drift leads to more modest increases in seasonal mortality.

The authors raised several more interesting points in their article:

• Influenza pandemics over several centuries have shown a big variation in severity, ranging from mild to severe.
• The new swine flu virus is a fourth-generation descendant of the 1918 virus.
• It appears that successive pandemics and pandemic-like events generally appear to be decreasing in severity over time. They say this is probably due to medical and public health advances.

What is the implication and importance of this?

This report helps to explain the evolution of the current pandemic strain of influenza virus, an area where extensive study can be expected. Although the genetic code of this virus has already been sequenced, this type of research may help in the search for effective vaccines, which remain the best hope for minimising the complications expected.
 
The authors say that while “we must be prepared to deal with the possibility of a new and clinically severe influenza pandemic caused by an entirely new virus, we must also understand [the current pandemic] in greater depth” and continue to “explore the determinants and dynamics of the pandemic era in which we live."