Writing today (Oct. 7, 2004) in the journal Nature, virologist Yoshihiro Kawaoka of the University of Wisconsin-Madison and the University of Tokyo, describes experiments in which engineered viruses were made more potent by the addition of a single gene. The work is evidence that a slight genetic tweak is all that is required to transform mild strains of the flu virus into forms far more pathogenic and, possibly, more transmissible.
The results of the new work promise to help scientists understand why the 1918 pandemic, a worldwide outbreak of influenza that killed 20 million people, spread so quickly and killed so efficiently, says Kawaoka, who has studied influenza viruses for 20 years. The finding also lends insight into the ease with which animal forms of the virus, particularly avian influenza, can shift hosts with potentially catastrophic results.
"Replacing only one gene is sufficient to make the virus more pathogenic," says Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine. In the Nature paper, Kawaoka and his colleagues describe how a Spanish flu gene that codes for a key protein changed a relatively benign strain of flu virus from a nuisance to a highly virulent form.
In the late 1990s, scientists were able to extract a handful of genes from the 1918 virus by looking in the preserved lung tissue of some of the pandemic's victims. Subsequently, the genes were sequenced, including two critical genes that make hemagglutinin and neuraminidase, the protein keys that help the virus enter and infect cells.
Using a comparatively mild form of influenza A virus as a template, Kawaoka's team added the two 1918 gen
Contact: Yoshihiro Kawaoka
University of Wisconsin-Madison