Study sheds new light on the cause of flu epidemics

Washington, March 5 : Penn State biologists say that the exchange of genetic material between two closely related strains of the influenza A virus might have led to the outbreak of human flu epidemics in 1947 and 1951.

The researchers say that their findings may prove helpful in discerning why some viral strains cause major pandemics, while others lead to seasonal epidemics.

Generally, it is believed that reassortment - when human influenza viruses swap genes with influenza viruses that infect birds - cause severe pandemics, while viral mutation leads to regular influenza epidemics.

However, it has been a mystery as to why there are sometimes very severe epidemics - like the ones in 1947 and 1951 - that look and act like pandemics, without there being a human-bird viral reassortment.

"There was a total vaccine failure in 1947. Researchers initially thought there was a problem in manufacturing the vaccine, but they later realized that the virus had undergone a tremendous evolutionary change. We now think that the 1947 virus did not just mutate a lot, but that this unusual virus was made through a reassortment event involving two human viruses," said Martha Nelson, lead author and a graduate student in Penn State's Department of Biology.

"So we have found that the bipolar way of looking at influenza evolution is incorrect, and that reassortment can be an important driver of epidemic influenza as well as pandemic influenza. We have discovered that you can also have reassortment between viruses that are much more similar, that human viruses can reassort with each other and not just with bird viruses," said Nelson, whose team's findings appear in the current issue of PLoS Pathogens.

In a study, Nelson's team analysed the evolutionary patterns in the H1N1 strain of the influenza A viruses by looking at 71 whole-genome sequences sampled between 1918 and 2006, and representing 17 different countries on five continents.

The genome data was used to construct phylogenetic trees that represented evolutionary relationships across all eight genome segments of the virus.

The researchers said that big differences in the shapes of the eight trees suggested that reassortment events had occurred.

According to them, the swapping of genes between two closely related strains of the influenza A virus through reassortment may also have caused the 1951 epidemic, which looked and acted in many ways like a pandemic as well.

So far three viral strains - H1N1, H2N2, and H3N2 -have infected humans. Scientists believe that understanding how each strain evolves over time is crucial.

Nelson says that this study shows that the evolution of a virus is not limited to the mutation of single lineage, and that there are multiple strains co-circulating and exchanging genetic material. The H1N1 and H3N2 strains, for instance, are occasionally generating hybrid H1N2 viruses.

"If we really want effective vaccines each year, our surveillance has to be much broader than simply looking at one lineage and its evolution, and trying to figure out how it is going to evolve by mutation. You have to look at a much bigger picture," said Nelson.

ANI