Thursday, May 26, 2011

You Say You Want An Evolution?




# 5576



One of the topics we return to in this blog with some frequency is the potential for pigs – which are susceptible to a variety of swine, human, and avian influenza viruses - to serve as `mixing vessels’ and to generate new influenza strains.


Since pigs can be infected by more than one flu virus at the same time, the potential exists for two viruses to swap genetic material (reassort), resulting in a new hybrid strain.

Reassortant pig[6]


The pandemic virus that emerged in the spring of 2009 was the end product of several influenza strains that had kicked around the world’s swine population for many years, trading bits of genetic material back and forth, until they produced a version capable of jumping to humans.


In the not-too-distant past, pigs were usually raised and slaughtered locally.


Over the past couple of decades, however, the cross country - and even international – shipping of live hogs has become a big business.  


According to Dr. Michael Greger’s excellent Flu Factories video presentation, pigs raised in the United States often travel hundreds of miles `on the hoof’, with many being `bred in North Carolina,  fattened in the corn belt of Iowa, but slaughtered in California’.


Which means that a swine virus that emerges in North Carolina could easily spread across the nation, carried either by live pigs, or on contaminated transport vehicles.


Internationally, live hogs are often shipped for breeding purposes, to inject genetic diversity into local herds to improve the breed.


Unfortunately, this practice has also increased viral diversity as well, introducing North American and European flu stains to places like China.


All of which serves as prelude to a study which was published yesterday in the Journal Nature, that takes the most extensive look to date at the introduction and evolution of swine flu viruses in China over the past 12 years (supplemented by data going back 34 years).


This report has an impressive pedigree, including such familiar names in the world of influenza virology as Kennedy F. Shortridge, Richard J. Webby, Robert G. Webster, Yi Guan  and  J. S. Malik Peiris.



Long-term evolution and transmission dynamics of swine influenza A virus

Dhanasekaran Vijaykrishna,Gavin J. D. Smith, Oliver G. Pybus, Huachen Zhu, Samir Bhatt, Leo L. M. Poon, Steven Riley, Justin Bahl, Siu K. Ma, Chung L. Cheung, Ranawaka A. P. M. Perera, Honglin Chen, Kennedy F. Shortridge, Richard J. Webby, Robert G. Webster, Yi Guan & J. S. Malik Peiris



Although the study is, lamentably, not open access, we’ve a number of resources giving us overviews of what was found.


First stop is a press release from the NIH/NIAID, which partially funded this work.


Evolution of swine flu viruses traced in long-term study

NIH-funded project yields baseline for better understanding of human influenza

Although swine influenza viruses usually sicken only pigs, potentially one might also spark a pandemic in people, as occurred with the 2009 H1N1 influenza virus. Because few long-term studies have surveyed flu viruses in swine, however, gaps exist in what is known about the evolution of swine influenza viruses and the conditions that enable a swine virus to infect humans and cause disease.


In new research reported in Nature, scientists analyzed the genetic makeup of more than 650 influenza viruses isolated during the systematic surveillance of pigs slaughtered in Hong Kong between 1998 and 2010. When the investigators supplemented this information with additional data stretching back 34 years, they could discern when specific subtypes of flu virus—including strains that had previously infected only birds or humans—first appeared in Hong Kong swine.


The researchers also traced the relative abundance of each of three major swine influenza virus lineages: classical, Eurasian avian-like and triple reassortant. Examples of all three of these long-established virus family lineages were found in varying proportions in samples gathered between 2002 and 2009. Before 2003, the classical lineage predominated; by 2005, the Eurasian lineage, first detected in 2001, had become most common. The most recent samples contain not only viruses from the three previously established swine lineages, but also from the new 2009 H1N1 strain. It is not yet known whether the new pandemic strain will permanently establish itself in swine.


According to this analysis, the three swine influenza virus lineages have crossed geographic boundaries, including continents. Such extensive co-circulation of multiple strains facilitates gene-swapping between viruses, note the researchers, and they recommend continued surveillance of swine influenza genetic diversity to better understand how this process might give rise to variants with the potential to cause human flu epidemics. Their baseline data not only show the evolutionary dynamics in swine influenza, but also highlight ways in which swine flu viruses might most readily adapt to cause infection in people.


CIDRAP , as part of their daily news scan, has a brief report on this as well (excerpted, and slightly reformatted for readability).


Imports helped swine flu in Hong Kong pigs to diversify

Importing pigs from Europe and North America over the past 30 years appears to have increased the genetic diversity of swine influenza in Hong Kong pigs through gene reassortment, according to a study today in Nature.




The authors write, "Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically diverse virus population."


Vijaykrishna Dhanasekaran, PhD, of Duke University, a study co-author, said the increased genetic diversity "means that the repertoire of viruses that humans are in contact with every day has increased, and this may lead to a higher likelihood of swine-to-human transmission, although the risk remains unquantified."



Duke University Medical Center – a participant in this study – has also put out a press release.



Long-term study of swine flu viruses shows increasing viral diversity

DURHAM, NC and SINGAPORE – Increased transportation of live pigs appears to have driven an increase in the diversity of swine influenza viruses found in the animals in Hong Kong over the last three decades, according to a new study.


In the longest study of its kind, Duke-NUS Graduate Medical School researchers found that swine viruses crossed geographic borders and mixed with local viruses, increasing their diversity.


(Continue . . . )



While this data is both vital and welcome, for most of the developing world, little or no viral surveillance of pigs takes place.


Even in the U.S. some hog farmers are reluctant to allow their herds to be tested (see Swine Flu: Don’t Test, Don’t Tell) out of fears that the discovery of a new swine flu virus would depress pork sales.


Some will only consent to anonymous testing, which limits the CDC’s ability to investigate cases.


Every once in awhile we get a report from somewhere in the world that a human has been infected with a novel influenza virus, usually of swine, avian - or quite often - mixed origin.  A few examples:


China: Single Novel Swine Flu Infection Reported

North America Influenza Surveillance - Week 4

CDC: Another Novel H3N2 Isolate


Rarely, as in the case of the 2009 swine flu virus, a novel strain adapts well enough to humans to spread efficiently through the population.


Most of the time, however, these are one-off type infections that are directly transmitted from an animal (pig, bird) to a single human.  Secondary transmission of the virus to others probably occurs, but only rarely and in a limited fashion.


But this serves as a constant reminder that nature’s laboratory is open 24/7, and viral evolution proceeds at remarkable speed.


For more background on influenza in swine, and the risks of reassortment, you can’t do better than  Helen Branswell’s excellent Scientific American article from last December called Flu Factories, or her SciAm Podcast.


You may also wish to revisit.


Hong Kong: Influenza Surveillance In Pigs
EID Journal: Swine Flu Reassortants In Pigs
The (Swine) Influenza Reassortment Puzzle
If You’ve Seen One Triple Reassortant Swine Flu Virus . . .

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