Flu: a ninety-year pandemic

Bethseda, Maryland – The influenza virus of 1918-1919 founded a viral dynasty that persists to this day – in fact, we’ve been living in a pandemic era ever since, according to scientists from the National Institute of Allergy and Infectious Diseases (NIAID).

The researchers say that the novel 2009 H1N1 virus now circling the globe is yet another manifestation of this enduring viral family.

“The 1918-1919 influenza pandemic was a defining event in the history of public health,” says NIAID Director Dr. Fauci. “The legacy of that pandemic lives on in many ways, including the fact that the descendents of the 1918 virus have continued to circulate for nine decades.”

Influenza viruses have eight genes, two of which code for virus surface proteins — hemagglutinin (H) and neuraminidase (N) — that allow the virus to enter a host cell and spread from cell to cell. There are 16 H subtypes and 9 N subtypes, and, therefore, 144 possible HN combinations. However, only three (H1N1, H2N2 and H3N2) have ever been found in influenza viruses that are fully adapted to infect humans. Other combinations, such as avian influenza H5N1, occasionally infect people, but they are bird viruses, not human viruses.

“The eight influenza genes can be thought of as players on a team: Certain combinations of players may arise through chance and endow the virus with new abilities, such as the ability to infect a new type of host,” says Dr David Morens, Senior Advisor to the NIAID Director.

This is probably what happened to spark the 1918 pandemic, he adds. Scientists have shown that the founding virus was an avian-like virus. The virus had a novel set of eight genes and — through still-unknown mechanisms — gained the ability to infect people and spread readily from person to person.

“All human-adapted influenza A viruses of today — both seasonal variations and those that caused more dramatic pandemics — are descendents, direct or indirect, of that founding virus,” notes Dr Jefferey Taubenberger, Senior Investigator in NIAID’s Laboratory of Infectious Diseases. “Thus we can be said to be living in a pandemic era that began in 1918.”

While the dynasty founded by the virus of 1918 shows little evidence of being overthrown, it does appear that successive pandemics and outbreaks caused by later generations of the 1918 influenza dynasty are decreasing in severity, notes Dr Morens. This is due in part to advances in medicine and public health measures, he says, but it may also reflect viral evolutionary pathways that favor increases in the virus’s ability to spread from host to host, combined with decreases in its tendency to kill those hosts.

“Although 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 in greater depth, and continue to explore, the determinants and dynamics of the pandemic era in which we live,” conclude the authors.

The article is published in the New England Journal of Medicine.