Mystery of pandemic flu virus of 1918 solved

Researchers have now provided the most conclusive answers yet to two of the world's foremost biomedical mysteries of the past century

A study led by Michael Worobey at the University of Arizona in Tucson not only sheds light on the devastating 1918 pandemic, but also suggests that the types of flu viruses to which people were exposed during childhood may predict how susceptible they are to future strains, which could inform vaccination strategies and pandemic prevention and preparedness.

Worobey and his colleagues developed an unprecedentedly accurate molecular clock approach and used it to reconstruct the origins of the 1918 pandemic H1N1 influenza A virus (IAV), the classical swine H1N1 influenza virus and the post-pandemic seasonal H1N1 lineage that circulated from 1918 until 1957.

Surprisingly, they found no evidence for either of the prevailing hypotheses for the origin of the 1918 virus - that it jumped directly from birds or involved the swapping of genes between existing human and swine influenza strains. Instead, the researchers inferred that the pandemic virus arose shortly before 1918 upon the acquisition of genetic material from a bird flu virus by an already circulating human H1 virus - one that had likely entered the human population 10-15 years prior to 1918.

If these individuals had been already been exposed to an H1 virus, it could explain why they experienced much lower rates of death in 1918 than those who died in greatest numbers, a cohort centered on those about 29 years of age in 1918.

IAV typically kills primarily infants and the elderly, but the pandemic virus caused extensive mortality in those ages 20 to 40, primarily from secondary bacterial infections, especially pneumonia.

The authors suggest that this is likely to be because many young adults born from about 1880 to 1900 were exposed during childhood to a putative H3N8 virus circulating in the population, which featured surface proteins distinct to both the major antigenic proteins of the H1N1 virus.

The study is set to be published in the Proceedings of the National Academy of Sciences (PNAS).