Wednesday, December 19, 2007

The Reassortment Tango

 

# 1389

 

 

Influenza viruses mutate and change constantly, although most of the time, the changes are small, incremental ones.  Every once in awhile, two viruses meet up and swap genetic segments (reassortment), and the result is a big change: a novel influenza virus.

 

Today we are hearing about a new virus, a mammalian adapted H2N3 virus, isolated in swine at two separate farms in 2006.   Previously, the H2N3 virus was only known to infect birds. 

 

This is important because anytime an avian influenza virus jumps the species barrier, it bears watching.

 

First the article, then some background.

 

 

 

New Swine Flu Has Avian Flu Genes

By Staff

 

(AXcess News) Washington - Researchers have identified a new strain of swine influenza--H2N3--which belongs to the group of H2 influenza viruses that last infected humans during the 1957 pandemic. This new strain has a molecular twist: It is composed of avian and swine influenza genes.

 

Agricultural Research Service (ARS) veterinarians Juergen Richt, Amy Vincent, Kelly Lager and Phillip Gauger conducted this research with Iowa State University (ISU) visiting scientist Wenjun Ma, ISU veterinarian Bruce Janke and other colleagues at the University of Minnesota and St. Jude Children’s Research Hospital. The ARS veterinarians work at the agency's National Animal Disease Center in Ames, Iowa.

 

The research team studied an unknown pathogen that in 2006 infected two groups of pigs at separate production facilities. Both groups of pigs used water obtained from ponds frequented by migrating waterfowl.

 

Molecular studies indicated the unknown pathogen was an H2N3 influenza virus that is closely related to an H2N3 strain found in mallard ducks. But this was the first time it had been observed in mammals.

 

Influenza viruses have eight gene segments, all of which can be swapped between different virus strains. Two of these gene segments code for virus surface proteins that help determine whether an influenza virus is able to infect a specific host and start replicating--the first step in the onset of influenza infection.

 

In the newly isolated swine H2N3, the avian H2 and N3 gene segments mixed with gene segments from common swine influenza viruses. This exchange--and additional mutations--gave the H2N3 viruses the ability to infect swine. Lab tests confirmed that this strain of H2N3 could also infect mice and ferrets.

 

These findings provide further evidence that swine have the potential to serve as a "mixing vessel" for influenza viruses carried by birds, pigs and humans. It also supports the need to continue monitoring swine--and livestock workers--for H2-subtype viruses and other influenza strains that might someday threaten swine and human health.

 

Results of this study were published online this week in the Proceedings of the National Academy of Sciences of the United States of America.

 

ARS is the U.S. Department of Agriculture's chief scientific research agency.

 

 

When veterinarians attended to two separate outbreaks of respiratory disease in swine farms located 4 miles apart in April and September of 2006, they had no idea they were dealing with a new, novel influenza virus. 

 

Attempts to match this virus to existing strains at the Minnesota Veterinary Diagnostic Laboratory (MVDL) failed, and the two viruses, named A/Swine/FarmA/22454/2006 and A/Swine/FarmB/49644/2006, were forwarded to the NADC for sequencing and to St. Jude for serotyping.

 

In the paper by Gramer, M., Goyal, S., Patnayak, D., Lager, K., Ma, W., Vincent, A., Richt, J., Webby, R. 2007.Isolation of reassortant H2N3 avian/swine influenza virus from pigs in the United States [abstract]. American Association of Veterinary Laboratory Diagnosticians 50th Annual Conference. p. 122.  the authors describe what happened next. 

(Reparagraphed for readability)

 

 

Through full genomic sequencing of the eight RNA segments of each virus, the viruses were subtyped as H2N3 influenza viruses with HA and neuraminidase (NA) genes of avian origin. Serotyping with ferret anti-duck H2N3 antisera was positive for both viruses. This is the first description of avian/swine H2N3 influenza virus isolated from pigs in the United States.

 

This is the first description of avian/swine H2N3 influenza virus isolated from pigs in the United States. The introduction of the virus into the swine farms is thought to be through the use of surface (pond) water used in the swine barns.

 

The ponds used as water supplies for both Farms A and B are frequented by migrating waterfowl in the spring and fall of each year.

 

The H2N3 viruses continue to circulate in both Farms A and B as indicated by positive (>1:40) H2N3 antibody titers found in sera collected from replacement breeding gilts and weaned pigs 6 months or more after onset of disease.

 

The impact of this virus on swine health and disease control strategies will be monitored through expanded swine influenza virus surveillance and characterization efforts.

 

Reassortment, or the swapping of gene segments between influenza viruses, is believed to be one of the mechanisms by which novel pandemic viruses arise.  Fortunately, there is no indication that this new virus has an affinity for humans. 

 

Of course, that could change over time.

 

The 1918 pandemic was caused by the H1N1 virus, which replaced whatever happened to be the dominantly circulating virus of that time.  For nearly 40 years, H1N1 circulated around the world as seasonal flu, until in 1957, a new flu erupted out of China.  

 

H2N2, or the Asian Flu.

 

Whenever a new, virulent flu emerges it usually wipes out its predecessor.  For eleven years, the H2N2 virus circulated until it too was replaced by the Hong Kong Flu, or H3N2 virus, in 1968. 

 

The 1957 and 1968 pandemics are believed to have arisen from reassortment events, where the existing seasonal flu, and an avian flu, swapped genetic material.   The reason both of these pandemics were less severe than 1918 is believed to be because both were caused by a virus that contained some human flu genetic material.

 

In other words, they were hybrids. Human/avian combinations.

 

The 1918 Spanish flu was so devastating because it was a wholly avian flu virus that adapted to humans.

 

Just as we fear the H5N1 virus is doing today. 

 

Currently we have two influenza A viruses roaming the globe, the H3N2 from the last pandemic, and H1N1 (yes, the virus that reigned supreme between 1918 and 1957) which quite surprisingly resurfaced in 1977.   There has always been speculation that the H1N1 virus may have been re-released due to a lab accident in the Soviet Union.

 

Since most of the world's population still carried some immunity to the H1N1 virus, it didn't push the H3N2 virus out of the way.  Instead, they both co-exist and circulate the globe today.

 

If all of this seems like some kind of gigantic genetic crapshoot, I suppose it is.  Viruses constantly mix and mingle, trading bits and pieces of their genetic code.  Most of the time, these mutations are dead ends.  Viral duds that are incapable of infecting or spreading efficiently.

 

But every once in awhile they end up creating something novel and very, very dangerous to mankind.

 

And so we remain vigilant, and hopefully prepared. 

 

For we know it will happen again.

1 comment:

Dipl.-Ing. Wilfried Soddemann said...

"Both groups of pigs used water obtained from ponds frequented by migrating waterfowl. ...
These findings provide further evidence that swine [wild boar too!] have the potential to serve as a "mixing vessel" for influenza viruses carried by birds, pigs and humans. ...
The introduction of the virus into the swine farms is thought to be through the use of surface (pond) water used in the swine barns.
The ponds used as water supplies for both Farms A and B are frequented by migrating waterfowl in the spring and fall of each year."

H5N1 avian flu: Spread by drinking water into small clusters:

Human to human and contact transmission of influenza occur - but are overvalued immense. In the course of Influenza epidemics in Germany recognized clusters are rarely (9% of the cases in the season 2005).
In temperate climates the lethal H5N1 avian flu virus will be transferred to humans strong seasonal in the cold via cold drinking water, as with the birds feb/mar 2006.
Recent research must worry: So far the virus had to reach the bronchi and the lungs in order to infect humans. Now it infects the upper respiratory system (mucous membranes of the throat e.g. when drinking and mucous membranes of the nose and probably also the conjunctiva of the eyes as well as the eardrum e.g. at showering). In a few cases (Viet Nam, Thailand) stomach and intestine by the H5N1 virus were stricken but not the bronchi and the lungs. The virus might been orally taken up, e.g. when drinking contaminated water.
The performance to eliminate viruses of the drinking water processing plants in Germany regularly does not meet the requirements of the WHO and the USA/USEPA. Conventional disinfection procedures are poor, because microorganisms in the water are not in suspension, but embedded in particles. Even ground water used for drinking water is not free from viruses.
In temperate climates the strong seasonal waterborne infections like norovirus, rotavirus, salmonellae, campylobacter and - differing from the usual dogma - influenza are mainly triggered by drinking water dependent on the drinking water temperature (in Germany minimum feb/mar – maximum august). There is no evidence that influenza primary is transmitted by saliva droplets. In temperate climates the strong interdependence between influenza infections and environmental temperatures can’t be explained with the primary biotic transmission by saliva droplets from human to human with temperatures of 37.5°C. There must be an abiotic vehicle like cold drinking water. There is no other appropriate abiotic vehicle. In Germany about 98% of inhabitants have a central public water supply with older and better protected water. Therefore in Germany cold water is decisive to virulence of viruses.
In hot climates/tropics the flood-related influenza is typical after extreme weather and natural after floods. Virulence of Influenza virus depends on temperature and time. If young and fresh H5N1 contaminated water from low local wells, cisterns, tanks, rain barrels or rice fields is used for water supply water temperature for infection may be higher as in temperate climates.

Dipl.-Ing. Wilfried Soddemann
eMail soddemann-aachen@t-online.de
http://www.dugi-ev.de/information.html
Epidemiological Analysis:
http://www.dugi-ev.de/TW_INFEKTIONEN_H5N1_20071019.pdf