Genome sequencing shows A.I. mutating

by Keith Nunes
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COLLEGE PARK, MD. — In the May issue of Emerging Infectious Diseases, an international team of researchers report the first ever large-scale sequencing of western genomes of the deadly avian influenza (A.I.) virus, H5N1. Their study of 36 genomes of the virus collected from wild birds in Europe, the Middle East and Africa (E.M.A.), and Vietnam confirms not only that the virus has very recently spread west from Asia, but that two of the new western strains have already independently combined, or "re-assorted," to create a new strain.

Several samples also contained the mutation associated with the form of A.I. that caused several human deaths in 2006. It is the virus’s ability to rapidly mutate into a pathogen that may eventually be passed between humans that concerns health officials about a worldwide pandemic of H5N1 influenza.

The study also produced some evidence that strengthens the case that humans have had an impact on the movement of the flu out of Asia.

"This is the first time anyone’s looked at all of the H5N1 genomes in the west," said Steven Salzberg, the study’s lead author and director of the University of Maryland Center for Bioinformatics and Computational Biology. "Until now, the studies have been primarily on samples from the Far East. Our study shows that the virus is spreading west, and that there have been three separate introductions of H5N1 in Europe, the Middle East and Africa."

The researchers collaborated to share data and sequence H5N1 samples taken from birds in a widely dispersed geographic region that included Nigeria, Niger, Sudan, Egypt, Afghanistan, Iran, Slovenia, Croatia and Italy.

"We found that the E.M.A. strains of the virus are distinct from the Vietnamese and other Asian strains," Mr. Salzberg said, "and that they have already divided into three separate new strains. One of the new strains has been the cause of several fatal human cases in Egypt and Iraq."

The research showed that the three new strains, called "clades," evolved independently and in different regions from a single genetic source.

"Our analysis places this source most recently in either Russia or Quinghai Province in China," Mr. Salzberg said.

The study showed that the new Euro-African lineage, which was the cause of fatal human infections in Egypt and Iraq in 2006, has been introduced at least three times into the E.M.A. region and has split into three distinct, independently evolving lineages. Two of those sub-lineages have recently re-assorted.

The broad dispersal of the different forms of the virus throughout the different countries over a relatively short period of time points to the possibility of human movement, rather than wild birds as the reason for the quick spread of the H5N1.

"The migratory pathways of wild birds don’t correspond with the movement of the genomes that we sequenced," Mr. Salzberg said. "Humans carry chickens between many of the countries in our study, often transporting them across great distances. That and the weak biosecurity standards in most rural areas point to human-related movement of live poultry as the source of the introduction of H5N1 in some countries."

While the study "dramatically increased the number of genomes that have been sequenced, we have to do more surveys," Mr. Salzberg said. "It’s surprising that we found what we did with such a small sample."

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