The outbreak of H1N1 influenza A virus that started in Mexico in recent weeks has been of great concern internationally. The National Pork Board (NPB) and the American Association of Swine Veterinarians (AASV) have provided excellent resource materials for dealing with the issues related to this outbreak: (www.pork.org/NewsAndInformation/WebFeaturePage2.aspx?Id=472 and www.aasv.org/).

You are encouraged to follow these recommendations and to work closely with your veterinarian as questions and concerns regarding influenza arise.

There are also some technical diagnostic questions that should be considered in light of this outbreak. Following are some producer questions that have come up at the diagnostic laboratory the past week. Many questions remain unanswered at this point, and the electronic rumor mill is probably about ready to blow a hard drive from the weight of all the misinformation spinning about. We hope these answers will provide some of the information you need.

Can pigs get infected with the new H1N1 virus?
The short answer is – we don’t know for sure. To date, this virus has not been detected in pigs anywhere. However, based on the genetic makeup of the virus, it appears likely that pigs could become infected with this virus. U.S. Department of Agriculture (USDA) veterinary research scientists are investigating whether pigs can be infected with this virus and what effect the virus has on pigs if they can be infected. These results won’t be available for at least a few weeks.

If this virus gets into pigs, will it be detectable by existing diagnostic tests?
Yes, our existing diagnostic tests are designed to detect all influenza A viruses, the group of viruses to which the new H1N1 strain belongs. Veterinary diagnostic laboratories can use virus isolation, polymerase chain reaction (PCR) tests and other methods to detect the virus.

Do we have tests that can differentiate this virus from other swine flu viruses?
Yes, the laboratories can look at the genetic makeup of the virus and determine if it is similar to the new H1N1 strain or if it resembles other influenza viruses. However, serology tests that detect antibodies against the influenza virus are not likely to be able to distinguish between exposures to the new virus vs. older viruses.

Are we testing pigs in the United States to make sure we don’t have this virus here?
Yes. Research veterinarians have been routinely characterizing swine influenza viruses for several years to understand how the virus changes over time and help direct disease control efforts. We presented a summary of influenza data from the Minnesota and Iowa veterinary diagnostic laboratories two months ago in the Swine Health Preview column (enews.penton.com/enews/nationalhogfarmer/north_american_preview_0/2009_march_6_north_american/display).

In addition, programs for ongoing surveillance to detect new strains of influenza in pigs and birds were established previously in response to concerns over the H5N1 influenza risk from birds. Specifically, we collaborate with the Centers for Disease Control and Prevention (CDC), the National Institutes for Health (NIH) and the USDA on influenza surveillance projects. These projects include sequencing avian viruses found in domestic and wild bird populations and swine influenza viruses found in domestic swine. This surveillance information is the basis for our belief that the new H1N1 influenza virus is not present in our swine populations.

Also, veterinary diagnostic laboratories across the United States are testing recent case submissions from pigs with respiratory disease to determine whether the new virus is present. As indicated in the resource material from the Pork Board and AASV, producers are encouraged to contact their veterinarian if they observe flu signs in their pigs: cough, snotty noses, fevers or lethargy.

The veterinarian will collect samples and submit them to the diagnostic lab to test for influenza and other causes of pneumonia. You can help your veterinarian by checking the temperature of pigs showing signs of respiratory disease. Submitting samples from pigs with a fever improves our chances of detecting viruses. Treating pigs with antibiotics doesn’t interfere with detecting viruses.

This virus is being called swine flu. Did it come from pigs?
This particular new H1N1 strain has not been found in pigs. Also, it is important to note that the investigations into the human illnesses have not been connected with pig exposure nor have there been reports of sick pigs with this virus.
That said, the question of the origin of the virus has frequently been raised by producers and the media.

The answer is fairly technical and has been somewhat controversial due to circulation of misinformation. To clarify, the genome of the influenza virus is made up of eight different genes. A graphic depiction of the influenza virus structure and the genome is shown in Figure 1 (attached). There are a lot of details in the figure, but the basic point is that the virus has eight genes, which are shown in the center of the virus structure. The history of these genes tells the story of the lineage of the virus.

So where did the virus come from?
We can answer questions about the ancestry, but we can’t say at this point in which species (pigs/people/birds) the new virus first developed.

The new H1N1 virus is a hybrid of genes that were contributed over time through a process called reassortment from swine, human and bird flu virus ancestors. This is illustrated in Figure 2 (attached). Of the eight different genes in the virus, one (PB1) has a human virus ancestor, two (PB2 & PA) have avian flu ancestors and the other five are from swine flu virus ancestors.

However, it’s a little more complicated than that. The human-like gene, both avian-like genes and two of the swine-like genes (NP & NS1 + NS2 ) have existed in a combination known as “triple reassortant internal genes (TRIG)” in flu strains seen in North American pigs for at least six years. This means the reassortment occurred several years ago and this virus has remained in pigs since that time.
Among the remaining three swine-like genes, one gene (HA) can be traced to a swine flu virus first identified in pigs from Indiana in 2000. The final two (NA & M1 + M2 ) swine-like genes are from Eurasian strains that have never before been detected in pigs or people in North America.

Thus, the new H1N1 virus has components from six virus genes (three pig-like, two bird-like and one human-like) that have been observed in pigs in North America for several years, plus two Eurasian pig-like genes. Again, this virus has not been identified in pigs. However, the parentage (if not the grand-parentage) is from pig viruses.

How does influenza virus change so often?
The written history of influenza in humans goes back 2,500 years and the natural history certainly goes back much further than that. The mechanisms that have allowed influenza virus to survive over the centuries lie in its ability to change through two methods: 1) small alterations in the genome (genetic drift), and 2) large reassortments of genes (genetic shift).

Gradual changes in the genome of the virus occur over time due to “errors” or alterations in the genetic information encoded in the viral RNA during virus replication. If the alteration is advantageous to the survival of the virus, the change lives on. Changes continue over time, resulting in gradual genetic drift away from the original parent virus.

Reassortment is possible for flu viruses because of the structure of its genetic packaging. Influenza is a segmented RNA virus. This means that the genome is broken up into segments in which the eight genes are physically separated on the same single strand of RNA (Figure 2). If a particular animal is infected with more than one strain of flu virus at a particular point in time, a new virus can be produced if the viruses mix and match their genes (pulling “genetic cards” from each other’s deck, as it were) during the process of making genetic copies.

If the resulting virus is advantageous (a “good hand”), it is fit to survive and replicate and can live on to infect other individuals. This mechanism allows the virus to undergo dramatic, rapid changes that skirt immunity against the original virus and, in some cases, allow the virus to infect other species as well. This genetic shift is rarely successful, which accounts for the relatively few times in history we have seen pandemic influenza outbreaks.




Click to view graphs.

Marie Gramer, DVM and Jerry Torrison, DVM
University of Minnesota Veterinary Diagnostic Laboratory
torri001@umn.edu