HONG KONG (Reuters) - Flu viruses that sparked the three worst pandemics in the last century circulated in their near-complete forms for years before the catastrophes occurred, researchers in Hong Kong and the United States have found.

The H1N1 flu virus (red)in an image taken. REUTERS/Image courtesy of Yoshihiro Kawaoka/University of Wisconsin-Madiso/Handout

The H1N1 virus that sparked the Spanish flu of 1918-1919 circulated in swine and humans well before the pandemic started, and it did not come directly from birds as previously thought, they added. Instead, it was probably generated by genetic exchanges between flu viruses from swine and humans.

This contrasts sharply with previous studies which suggested that the H1N1 virus of 1918 was a mutant that jumped direct from birds to human and ended up killing as many as 50 million people.

The findings are considered important because of the lack of studies of the virus in animals before the current outbreak of H1N1. Through understanding the natural history of viruses, monitoring of current viruses can be fine-tuned, the team from the University of Hong Kong and St Jude Children’s Hospital in the United States wrote.

Published in the Proceedings of the National Academy of Sciences, the study also involved two other pandemic viruses

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the H2N2 responsible for the Asian flu of 1957, and the H3N2 which sparked the Hong Kong flu of 1968.

Guan Yi, microbiologist at the University of Hong Kong and member of the research team, said the viruses of 1918 and 1957 went through at least two rounds of reassortments before the pandemics occurred. Reassortments happen when flu viruses swap genetic material, which happens when an animal or person is infected with two strains at the same time.

“Before, people did not know how pandemic viruses came about ... this study gives us a deeper understanding into the evolution and emerging process of pandemic viruses,” Guan said.

Another finding was that the H1N1 pandemic virus of 1918, the seasonal H1N1 virus of today and the classical H1N1 swine virus may have been co-circulating in the 1918-1919 period.

“All three are different viruses but related ... which would explain why some waves of the (1918-1919) pandemic were more deadly than others,” Guan said.

The team analyzed and compared the genes of the 1918, 1957, and 1968 viruses and their close relatives to determine their ancestry and the gene exchanges that created them.

The genes of the 1918 virus likely circulated in swine and humans from as early as 1911, and the virus was unlikely to have been transmitted directly from birds to humans, Guan said.

“It is very difficult for viruses to jump directly from bird to human (and cause a pandemic), which may explain why the H5N1 virus hasn’t caused a pandemic so far (by making that direct jump from bird to human),” Guan said.

The H2N2 (1957) and H3N2 (1968) reassortant viruses formed similarly, through exchanges with unknown mammalian hosts and input from bird viruses.

“Because of a lack of sequence data for swine influenza from these periods, the involvement of swine in the generation of these pandemic strains cannot be precluded,” the paper said.