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New Genetic Technology IDs Virus That Killed Transplant Recipients
Date:2/6/2008

Could be used to help against many illnesses that evade diagnosis, experts say

WEDNESDAY, Feb. 6 (HealthDay News) -- A new genetic-sequencing technology has enabled the fastest-ever identification of a deadly virus, one that killed three transplant patients, researchers report.

The technique could be used to help against many common illnesses that now evade diagnosis, experts said.

"It is now possible to use this method, which is rapid and comprehensive, to find new pathogens in staggering time," said study senior author Dr. W. Ian Lipkin, professor of epidemiology at the Columbia University Mailman School of Public Health.

The virus struck three Australian women who received transplants from one donor -- two kidneys and a liver. All three began to run a high fever and died four to six weeks after the transplants. Researchers in Australia and the United States then used the new technology on samples of RNA, the genetic material used by viruses, taken from the three women.

More than 103,000 RNA sequences were analyzed by the new technology. Fourteen of them were found to be identical with that genetic material of an infectious agent called an arenavirus. Antibodies against that virus were then found in the bodies of the three women.

The study findings were released online Wednesday a month ahead of print in the New England Journal of Medicine.

The genetic-sequencing technology was developed by 454 Life Sciences, a Branford, Conn.-based biotechnology company that was recently bought by Roche Pharmaceuticals. Its speed has been demonstrated before, in more basic scientific work, said Brendon Hill, a spokesman for the company.

The Human Genome Project, the first effort to sequence the entire genetic material in human beings, took years and cost about $2.5 billion, Hill said. The new technology got the complete genetic sequence of James Watson, one of the discoverers of the common genetic material DNA, in less than a month for less than $1 million, he said. The technique has also been used to get a complete genetic sequence of Neanderthal man, he added.

In the case of the transplant infections, the technique compared the sequences of genetic material obtained from the infected women with a huge number of viral sequences until a match was found.

"That use is not just limited to transplants," Lipkin said. "If there is any unexpected outbreak, we can take this particular technique and use it to survey the entire tree of life."

A previous transplant mystery, in which seven U.S. recipients died in 2003 and 2005, was eventually solved with identification of lymphocytic choriomeningitis virus (LCMV), which is carried by hamsters and other rodents. The newly identified arenavirus is related to LCMV.

The previous identification "took hundreds of scientists across the world and weeks of work," Lipkin said. "With a technique like this, you can come to a diagnosis in a very few days."

The technology could be used to help solve an ongoing mystery that's being tackled by the U.S. Centers for Disease Control and Prevention's Unexplained Encephalitis Project, according to an accompanying editorial by Dr. Richard J. Whitley of the University of Alabama at Birmingham.

About 40 percent of Americans who have probable infections of the central nervous system never receive a diagnosis that establishes the cause of their illness, Whitley said. The same is true of up to 40 percent of the respiratory infections that kill about two million people worldwide each year, he said.

"This new application of metagenomic pyrosequencing may well aid in the identification of unknown microbial agents that cause human disease," Whitley wrote.

"The real story is the coming-of-age of a sophisticated, highly sensitive mass screening type of molecular diagnosis," added Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases. "It can be used not only for such things as this isolated mystery of a cluster of infections but also to search for a microbe in an infection in which one has not been detected."

More information

An explanation of genetic sequencing is provided by the Human Genome Project.



SOURCES: W. Ian Likpin, M.D., professor of epidemiology, Columbia University Mailman School of Public Health, New York City; Brendon Hill, spokesman, 454 Life Sciences, Branford, Conn.; Anthony Fauci, M.D., director, U.S. National Institute of Allergy and Infectious Diseases, Bethesda, Md.; March. 6, 2008, New England Journal of Medicine


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