Engineered hybrids of bird and human flu strains have proven virulent in mice, raising the disturbing possibility that a natural recombination could be deadly to humans.

For years, researchers have worried that H5N1 avian influenza would mix with human flu viruses, evolving into a form that keeps its current lethality but is far more contagious. That hasn't happened – but the latest findings, published Feb. 22 in the Proceedings of the National Academy of Sciences, show how easily it might.

"Fortunately, the H5N1 viruses still lack the ability to transmit efficiently among humans." However, this obstacle may be overcome by mixing with flu strains common in people, wrote researchers led by University of Wisconsin virologist Yoshihiro Kawaoka. "The next pandemic then will be inevitable."

Current strains of H5N1 have infected 478 people since 2003, and killed 286 of them. It's difficult to transmit in humans, requiring close contact with an infected person or animal. In birds, however, H5N1 is far more contagious, and his killed tens of millions of fowl. Cases have been concentrated in Africa and Eurasia, but as the swine flu pandemic demonstrated, any flu contagious to humans will likely go global, fast.

Influenza viruses swap genes easily, with co-infections turning animals into mobile petri dishes. In 2008, hoping to learn more about how H5N1 might evolve, researchers from the Centers for Disease Control and Prevention combined it with a common human flu strain. The hybrids proved less virulent than the original bird flu strain. Researchers wondered whether more contagious bird flu would necessarily always be less deadly in humans.

The PNAS findings suggest this may not be so. The researchers engineered all 254 possible variants of hybridization between a deadly bird flu strain found in Borneo, and a human flu virus from Tokyo. They identified three strains that, at least in mice, were both contagious and deadly.

A flu virus that kills mice won't necessarily kill humans, but the results are suggestive. All three killer hybrid strains possessed a protein taken from the human strain. Called PB2, the protein appeared to help the virus survive in the mice's upper respiratory tract. As of now, bird flu stays in the lower respiratory tract, where it's less likely to be casually transmitted.

The findings come as the World Health Organization meets to decide whether the swine flu pandemic has abated. Though the pandemic has not proved as lethal as originally feared, it exposed how unprepared the world is for new influenza strains.

In May, Hong Kong University virologist Yi Guan, best known for finding the animal origin of SARS, was asked by Science Insider about the possibility of H5N1 and swine flu mixing.

"If that happens, I will retire immediately and lock myself" in a sealed laboratory, said Guan.

Photo: A person feeds northern pintail ducks and whooper swans in Northern Honshu, Japan; in spring 2008, highly pathogenic H5N1 was found there in both bird species./USGS

See Also:

Citation: "Reassortment between avian H5N1 and human H3N2 inﬂuenza viruses creates hybrid viruses with substantial virulence." By Chengjun Li, Masato Hatta, Chairul A. Nidom, Yukiko Muramoto, Shinji Watanabe, Gabriele Neumann, and Yoshihiro Kawaoka. Proceedings of the National Academy of Sciences, Vol. 107 No. 8, February 23, 2010.

Brandon Keim's Twitter stream and reportorial outtakes; Wired Science on Twitter. Brandon is currently working on a book about ecological tipping points.