An interactive "supermap" that portrays the mutations and spread of the avian flu around the globe over time should help researchers and policy makers better understand the virus and anticipate further outbreaks, according to a new study involving University of Colorado at Boulder and Ohio State University researchers.
The research team used data from the known evolution and spread of the avian flu, known as H5N1, to create a roadmap of viral spread in time and space, said CU-Boulder ecology and evolutionary biology Assistant Professor Robert Guralnick, a study co-author. The team projected genetic and geographic information onto an interactive globe using Google Earth technology, allowing users to fly virtually around the planet and analyze movements and changes in the genomes, or genetic blueprints, of known avian flu sub-strains that have been sequenced since the virus was first detected in Guangdong, China, in 1996.
The researchers used the novel technology to chart the spread of H5N1 through Asia, Indonesia, the Middle East and Europe by various hosts, including its transport by specific orders of birds and mammals, said CU-Boulder graduate student Andrew Hill, a study co-author. They also used the supermap to track key genetic traits prevalent in some avian flu genomes that appear to confer the ability of H5N1 to more readily infect mammals, including humans, he said.
"This is a completely new method of integrating and sharing knowledge about disease spread, giving people a quick and easy way to make sense of the changes," said Hill, chief architect of the visualization portion of the collaborative research project. A paper by a team led by Daniel Janies of Ohio State University and involving Guralnick, Hill and American Museum of Natural History researchers Eric Waltari and Ward Wheeler is being published in the April issue of Systematic Biology.
Like the legend of a roadmap, colors and symbols on the supermap indicate which types of hosts carry the virus or the distribution of genotypes of interest, said Hill. "This allows us to test hypotheses on the geographic distribution of strains that contain what laboratory studies have suggested are the key genotypes that allow avian strains of the influenza virus to infect mammals," Hill said.
The team studied genomic sequence data from 351 different strains of the avian flu collected in the field, said Guralnick, who is also Curator of Invertebrate Zoology at the University of Colorado Museum. A click by users on viral "isolates" generates computer windows revealing diagnostic mutations that make each strain unique, and the information is linked by computer to the National Institutes of Health's GenBank, a database containing more than 75 million sequence records.
As part of the effort, the team looked at two key proteins found on the surface of H5N1 strains known as hemaglutinin, or HA, and neuraminidase, or NA. Scientists think if a virulent strain of H5N1 adapts to succeed at human-to-human transmission, it would likely involve mutations by the two proteins, said Guralnick. No mutations associated with NA and HA were linked to any specific bird or mammal host, he said.
But the team did find a strong association between a specific genotype, Lysine-627, in a segment of the viral genome called the polymerase basic protein, or PB2, and in mammalian hosts in the field. "While this genotype is not exclusive to mammals, we think it is important to track how this PB2 mutation is spreading because it appears to be so infective and deadly in mice," said Janies.
The team also used the supermap to visualize the spread of H5N1 in various parts of the world by specific orders of birds and mammals, including waterfowl, domestic fowl, shorebirds, raptors, songbirds, hoofed mammals and carnivores, said Guralnick.
In one instance the supermap shows a direct line spreading from Thailand to Europe in a single rapid event, illustrating a 2004 incident when several infected eagles were smuggled into Belgium, said Hill. While the birds were immediately seized and confined, preventing further spread, the supermap portrayal of the event illuminated how illicit wildlife trading can trigger huge leaps in virus transport.
The avian flu epidemic was first detected in wild aquatic birds in Guangdong in 1996 and spread to chickens and a few humans in Hong Kong by 1997. From 1997 to 2005, the virus emerged in several Southeast Asian countries and spread through multiple hosts to Japan, Korea, Russia the Middle East and India. In the past two years the virus has spread to Western Europe and reemerged in Korea.
While H5N1 is not highly communicable to humans or between humans, experts are concerned that future mutations have the potential to make the bird flu significantly more contagious. According to the World Health Organization, there have been 269 cases of the disease in humans since the initial outbreak in 1996, including 164 deaths. According to the Centers for Disease Control in Atlanta, an avian flu pandemic could infect 15 percent to 35 percent of the United States population and cost well over $100 billion.
Andrew Hill (cell) (720) 289-3894
Jim Scott, (303) 492-3114
April 30, 2007
Hill, a master's candidate in CU-Boulder's ecology and evolutionary biology department, began working on the mapping project as an undergraduate with Guralnick. The supermap project was funded by the Defense Advanced Research Projects Agency, and some of the sequencing was supported by the National Institutes of Health.
To access video about the Google Earth avian flu project, use your web browser to open the following link: http://researchnews.osu.edu/archive/flumap.mov.
A copy of the paper can be accessed by contacting Jim Scott at (303) 492-3114 or on the Web at: http://www.tandf.co.uk/journals/titles/10635157.asp.
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