Exploring Genetic Resistance to PRRS

Scientists are searching for disease resistance genes that could make it possible to someday select breeding animals that could pass natural PRRS virus resistance to their offspring.

Scientists are searching for disease resistance genes that could make it possible to someday select breeding animals that could pass natural PRRS virus resistance to their offspring.

Swine diseases cost U.S. producers more than $1.5 billion annually. Porcine reproductive and respiratory syndrome (PRRS) virus, the most economically significant infectious disease, costs the U.S. pork industry an estimated $600 million/year.

Current approaches to manage PRRS are costly and relatively ineffective as long-term solutions. The University of Nebraska is investigating selection for disease resistance as an alternative.

Previous disease research provides optimism that genes conferring resistance to PRRS exist. Natural resistance to certain diseases in laboratory animals and in humans is heritable, and genes that affect disease traits have been discovered.

Genetic variation in pigs for immune response to pseudorabies (PRV) and atrophic rhinitis vaccines has been reported. In a Canadian experiment, selection for general immune response was also effective.

The problem is that selection for disease resistance using traditional methods is difficult. Selection will be more effective once we have identified the genes that confer resistance. The major hurdle is the collection of informative disease records to segregate disease resistance genes to be traced in pedigrees. Once linkage has been established, genes can be located and direct selection for the good genes can be practiced.

With the help of a grant from the Nebraska Pork Producers Association, a project was initiated at the University of Nebraska with just such an objective. Four hundred pigs, 200 from the Nebraska Index (NEI) line and 200 Duroc-Hampshire (D-H) crosses, by 83 sires and 163 dams, were used. Half of the pigs were infected with PRRS virus at 26 days of age. A littermate to each PRRS-challenged pig served as a control.

Blood was drawn from each challenged pig on Days 0, 4, 7 and 14 to measure viremia, a measure of the pig's ability to replicate the virus. Body weight and body temperature were recorded each day. On Day 14, pigs were slaughtered, lungs were scored for lesions, and blood, lung, lymph and spleen tissue were collected.

Early Results Offer Clues

Although the results obtained so far are preliminary, and no conclusions about selection for PRRS resistance can be made, results indicate possible underlying genetic variation in response to the PRRS virus.

Body temperature was normal in unchallenged pigs, increasing from Day 0 to 14 in both populations (Figure 1). However, temperature in D-H pigs challenged with PRRS virus increased more rapidly and remained higher than in NEI line pigs, indicating that NEI pigs were more resistant to the effects of the virus.

This fact was supported by the pattern of growth (Figure 2). Unchallenged D-H pigs gained 1.5 lb., roughly 22% more, in 14 days than NEI pigs.

But quite a different response occurred in PRRS-challenged pigs. Pigs from both populations gained very little weight in the first seven days, but in the next seven days NEI pigs gained nearly twice as much weight as D-H pigs.

Viremia level, the number of plaque-forming colonies per deciliter (roughly 0.2 pint) of serum, was recorded as the base 10 logarithm of the actual number.

For example, an observation of 10 colonies is reported as 1 (10 raised to the power 1 equals 10, 101 = 10), 100 colonies are reported as 2 (102 = 100), 1,000 colonies as 3 (103 = 1000), etc. Differences in the exponent coefficients represent considerably greater differences in numbers of colonies.

Viremia level was significantly less for NEI pigs than D-H pigs. NEI pigs averaged 4.23, 3.99, and 3.23 colonies on Days 4, 7 and 14, respectively, compared with means of 4.52, 4.47 and 3.49 for D-H.

To put these differences in perspective, the coefficients of 4.23 and 4.53 for NEI and D-H pigs at Day 4 represent a twofold increase in the number of colonies (104.23 = 16,982 and 104.52 = 33,113).

The distribution of viremia across all pigs is in Figure 3. All pigs replicated virus, but some replicated it at a very low rate, whereas others had extremely high replication rates.

Sorting Out the Differences

The meaning of this variation is not clear yet, but several interesting patterns of performance associated with viremia were observed. Some pigs that replicated PRRS at high rates showed all the symptoms of PRRS (low weight gain, high temperature, lung lesions), while other pigs replicated PRRS virus at high rates, but showed only mild or no symptoms of PRRS. These pigs have tentatively been classed as “susceptible” and “tolerant,” respectively.

Then there were the other extremes. Pigs that replicated the virus at very low rates, and showed almost no symptoms of PRRS, were classified as “resistant,” and pigs that replicated the virus at low rates but showed mild to severe PRRS symptoms, were labeled “sensitive.” There were only 3-5 pigs in each of these extreme categories, but they are the ones that are the most interesting for further genetics research.

The researcher's goal is to isolate RNA from tissues collected from these pigs and look for genes that are expressed differently. RNA is the chemical that takes the message contained in the DNA, the chemical component of the gene, and puts the gene's action into effect in the animal's cells. The genes responsible for different responses to virus can be determined from the different RNA patterns in the cells of animals in each unique group. Tissue from the littermate controls will be used to determine whether expression differences are in response to the virus, or whether there are underlying genetic differences that are expressed independent of presence of PRRS virus.


Results at this point indicate that underlying genetic variation in response to PRRS exists. However, much work is still needed to determine the nature of this variation and how to best exploit it in a selection program. The goal is to be able to select directly for genes that confer natural resistance, or, through knowledge of the function of the genes involved, manipulate the pig's immune system to enhance resistance.