In more than one way, H7N9 influenza seriously caught public health experts by surprise. When the virus struck China earlier this year, it became the first flu strain from birds to stably infect humans since the 1918 Spanish influenza strain, which ultimately spread to half a billion people and killed about three to five percent of the world's population.

In a new mini-report from the journal mBio, public health experts from the National Institutes of Health (NIH), including the director of the Allergy and Infectious Disease unit, say there are multiple causes for concern over the possible reemergence of H7N9 given highlights from the history of avian influenza strains.

1. Poultry is a playground for H7 Influenza.

The first point highlights the fact that H7 influenza viruses love birds.

Influenza A viruses are classified by two proteins embedded in their outer coating: hemagglutinin (H) and neuraminidase (N). For example, there is H1N1, which caused 1918 pandemic, but is also a prominent strain with seasonal flu at the moment.

The authors point out that H7 strains have repeatedly caused massive outbreaks in wild birds and domestic poultry over the past 135 years. In every incident sans one, the infections have spilled over into humans. While prior strains have infected hundreds of people, H7N9 represented the first strain to be significantly lethal, killing 43 of 133 laboratory-confirmed cases as of July 4.

Wild birds are often infected with multiple avian influenza strains at once, offering a perfect breeding ground for the viruses to swap genes and potentially become more dangerous. During its spring outbreak, H7N9 didn't easily spread from human to human, but the authors worry that in the future, H7N9 could gain traits that boost its lethality.

2. The H7N9 - H5N1 Connection.

Moreover, H7N9 spread silently through poultry livestock, especially within markets, during its recent outbreak. This is in sharp contrast to the H5N1, which some regard as the bird flu virus with the greatest potential threat for an international pandemic. The two viruses share a number of clinical features, like multi-organ failure and acute respiratory disress, so it could be troublesome if H7N9 becomes more potent.

3. Who invited this pig to the party?

H7 influenza viruses have jumped into other mammalian species before, including horses and pigs. The latter raises greater concern, because like birds, pigs are a great "mixing vessel" for flu viruses, as evidenced by the H1N1 "swine flu" pandemic strain that struck Mexico in 2009.

For now, H7N9 is at bay, but no one knows how the virus will behave in the future. Luckily, this means that there is a window of opportunity for scientists to figure out the best way to stop the germ, if it should resurface during the upcoming flu season. (Ever wonder why flu season is in the winter, check out this great cartoon from Popular Science.)

"We have a unique opportunity to learn more of influenza's many secrets, and thereby enhance our ability to prevent and control an important disease that seems destined to appear again and again, in multiple guises, far into the foreseeable future," wrote the authors, who included Drs. David Morens, Jeffery Taubenberger, and Anthony Fauci of the NIH's National Institute of Allergy and Infectious Diseases.

Source: Morens DM, Taubenberger JK, Fauci AS. H7N9 Avian Influenza A Virus and the Perpetual Challenge of Potential Human Pandemicity. mBio. 2013.