Phylogeography Tracks Bird Flu?s Long March
28 Mar, 2007 11:48 am
?Appear at points which the enemy must hasten to defend; march swiftly to places where you are not expected.? -Sun Tzu, The Art of War (6th century BC).
A new study by scientists from the University of California, Irvine offers the first attempt at reconstructing H5N1’s march using the virus’s genetic code. The researchers combined genetic sequence data and information about the geographic localities from which study samples were taken to create maps of H5N1’s migration patterns.
The researchers showed that since 1996 multiple H5N1 strains have spread from the Chinese province of Guangdong to other provinces within China and internationally to other countries. In contrast, in Thailand and Vietnam, H5N1 dispersal appears largely limited to local areas.
The study was published in the March 13 edition of the Proceedings of the National Academy of Sciences (http://www.pnas.org/cgi/content/abstract/0700435104v1).
The study’s results may help intervention efforts. By learning where H5N1 strains repeatedly evolve and migrate, health officials can better plan for potential H5N1 incursions. Local vaccinations can be better administered using strains from regions that have previously contributed to outbreaks. Interventions may also take the form of regulating poultry imports and changing agricultural practices.
“If you can control the virus at its source, you can control it more efficiently,” said Walter Fitch, who led the study team. “With a road map of where the strain has migrated, you’re more likely to isolate the strain that you should be using to make the vaccine.”
Regions that may be acting as sources of repeated outbreaks may benefit as well.
“If Guangdong is indeed a source, a decision on the part of Chinese officials to intervene may very well help block outbreaks both within China and internationally,” said Robert Wallace, the lead author of the study. “Given the possibility of a pandemic, blocking the spread of bird flu to areas that can’t handle outbreaks is essential.”
With 192 publicly available genetic sequences isolated by other research groups from 20 localities across Eurasia through 2005, the UC Irvine team reconstructed what is in essence a family tree for the virus. With the family tree and knowledge of the region of isolation for each sample, the researchers were able to reconstruct the migration events that occurred from one locality to another through H5N1’s evolutionary history.
The phylogeography also permitted the scientists to offer new hypotheses about what may be a key mechanism in H5N1’s evolution and spread.
The family tree suggested H5N1 strains undergo parallel evolution, or the independent evolution of similar traits. Different strains appear to repeatedly evolve similar combinations of molecular changes in hemagglutinin, one of the two influenza proteins the researchers analyzed. The parallel evolution appears to allow H5N1 to switch across different host species.
Along with a variety of migratory and domestic bird species, H5N1 has infected several mammalian hosts, including humans, tigers, and pigs.
The parallel evolution and easy access to multiple hosts may provide H5N1 a means by which to spread more easily.
“Suppose H5N1 entered Mongolia by migratory bird,” said Wallace. “H5N1 may not be able to travel out of Mongolia that way. It might then switch to a host that is leaving town, maybe a batch of chickens packed on a train for southern Russia.”
The UC Irvine team is currently undertaking another analysis, including hundreds of more samples across a wider range of localities and through the year 2006.
“This was the first attempt at a statistically informed reconstruction of H5N1’s migration,” said Wallace. “We’ve got a good first sketch of H5N1’s marching orders, something we didn’t have before. Now we’re after a sharper picture of the roads bird flu frequents.”
H5N1, one of several deadly influenzas circulating among poultry, has killed millions of birds and infected 278 humans. Many experts think H5N1 has considerable potential for evolving into a human-to-human infection and starting a worldwide pandemic.
R. Wallace et. al., A statistical phylogeography of influenza. A H5N1 Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0700435104. 7, March 2007.
1Department of Ecology and Evolutionary Biology, University of California, 321 Steinhaus Hall, Irvine, CA 92697; and 2Donald Bren School of Information and Computer Sciences, University of California, 444 Computer Science Building, Irvine, CA 92697
The geographic diffusion of highly pathogenic influenza A H5N1 has largely been traced from the perspective of the virus's victims. Birds of a variety of avian orders have been sampled across localities, and their infection has been identified by a general genetic test. Another approach tracks the migration from the perspective of the virus alone, by way of a phylogeography of H5N1 genetic sequences. Although several phylogenies in the literature have labeled H5N1 clades by geographic region, none has analytically inferred the history of the virus's migration. With a statistical phylogeography of 192 hemagglutinin and neuraminidase isolates, we show that the Chinese province of Guangdong is the source of multiple H5N1 strains spreading at both regional and international scales. In contrast, Indochina appears to be a regional sink, at the same time demonstrating bidirectional dispersal among localities within the region. An evolutionary trace of HA1 across the phylogeography suggests a mechanism by which H5N1 is able to infect repeated cycles of host species across localities, regardless of the host species first infected in each locale. The trace also hypothesizes amino acid replacements that preceded the first recorded outbreak of pathogenic H5N1 in Hong Kong, 1997.