First large-scale bird flu genome study

Investigators at St. Jude Children's Research Hospital have completed the first large-scale study of bird flu virus genomes, thereby doubling the amount of genetic information available on the genes and proteins of these viruses.

The results of the project could lead to major insights into the bird flu virus known as H5N1, the researchers said. H5N1 is the bird flu virus currently infecting humans in Asia and Eastern Europe, and flu experts fear it could mutate in a way that would allow it to cause a worldwide pandemic in humans.

"These studies provide the first fundamental insight into the evolution of influenza viruses in nature -- the source of all influenza viruses that affect humans, domestic animals and birds," said Robert G. Webster, Ph.D., a member of the Infectious Diseases department and holder of the Rose Marie Thomas Chair at St. Jude. "This information is a true gold mine, and we are inviting all of the miners to help us unlock the secrets of influenza." Webster is an internationally renowned expert on bird flu viruses and a co-author of the report that appears in the January 27 issue of Science.

St. Jude was uniquely positioned to conduct these studies because it houses Webster's large collection of bird flu viruses collected over several decades. The hospital is also home to St. Jude's Hartwell Center for Bioinformatics and Biotechnology, which provided the necessary expertise and biotechnology resources; and its supercomputer has the horsepower needed to conduct these studies.

"Despite the major threat to human health posed by these viruses, there was very little information available on the entire genomes of bird flu viruses," said Clayton Naeve, Ph.D., director of St. Jude's Hartwell Center. "The St. Jude Influenza Virus Genome project provides a major contribution to our understanding of H5N1 and other bird flu viruses. Now we're in a much better position to understand what makes these viruses tick. And that could help us learn how to control the avian influenza viruses that threaten humans." Naeve is senior author of the report in Science.

The project produced 70 million bases of sequence information leading to DNA sequences for 2,196 genes and 169 complete bird flu genomes from the St. Jude collection, including representatives of all known subtypes of the virus including H5 bird flu. Preliminary analysis of these data and development of new analysis software has led to the discovery of new forms of bird flu genes, how these viruses evolve through time and the identification of genes that travel together through evolution. The St. Jude research also made an intriguing discovery that avian influenza viruses have a particular molecular feature that human influenza viruses do not have, which may cause them to be more toxic when infecting human cells.

"The major accomplishment of this project is that it gives the scientific community significantly more new data and analytical tools to use in the study of these potentially very dangerous viruses," said John C. Obenauer, Ph.D., a Bioinformatics associate research scientist at St. Jude's Hartwell Center. "In the future, that might lead to effective strategies for controlling outbreaks of these viruses in birds and humans." Obenauer is first author of the paper.

Other authors of the paper include Jackie Denson, Perdeep K. Mehta, Xiaoping Su, Suraj Mukatira, David B. Finkelstein, Xiequn Xu, Jinhua Wang, Jing Ma, Yiping Fan, Karen M. Rakestraw, Erich Hoffmann, Scott Krauss, Jie Zheng and Ziwei Zhang.

This work was primarily funded by ALSAC, the St. Jude fund-raising arm, with additional support from the National Institutes of Health, a Cancer Center Support grant and the Hartwell Foundation.