Control of porcine reproductive and respiratory syndrome (PRRS) through genetic improvements in disease resistance and tolerance

Abstract

Infections caused by porcine reproductive and respiratory syndrome virus (PRRSV) have a severe economic impact on pig production in North America, Europe, and Asia. The emergence and eventual predominance of PRRS in the 1990s are the likely result of changes in the pork industry initiated in the late 1970s, which allowed the virus to occupy a unique niche within a modern commercial production system. PRRSV infection is responsible for severe clinical disease, but can maintain a life-long subclinical infection, as well as participate in several polymicrobial syndromes. Current vaccines lessen clinical signs, but are of limited use for disease control and elimination. The relatively poor protective immunity following vaccination is a function of the virus's capacity to generate a large degree of genetic diversity, combined with several strategies to evade innate and adaptive immune responses. In 2007, the PRRS Host Genetics consortium (PHGC) was established to explore the role of host genetics as an avenue for PRRS control. The PHGC model for PRRS incorporates the experimental infection of large numbers of growing pigs and has created the opportunity to study experimental PRRSV infection at the population level. The results show that pigs can be placed into distinct phenotypic groups, including pigs that show resistance (i.e., low virus load) or pigs that exhibit "tolerance" to infection. Tolerance was illustrated by pigs that gain weight normally in the face of a relatively high virus load. Genome-wide association analysis has identified a region on chromosome 4 (SSC4) correlated with resistance; i.e., lower cumulative virus load within the first 42 days of infection. The genomic region is near a family of genes involved in innate immunity. The region is also associated with higher weight gain in challenged pigs, suggesting that pigs with the resistance alleles don't seem to simultaneously experience reduction in growth, i.e., that resistance and tolerance are not antagonistically related. These results create the opportunity to develop breeding programs that will produce pigs with increased resistance to PRRS and simultaneously high growth rate. The identification of genomic markers involved in actual tolerance will likely prove more difficult, primarily because tolerance is difficult to quantify and because tolerance mechanism are still poorly understood. Another avenue of study includes the identification of genomic markers related to improved response following vaccination.

Keywords: PRRS resistance; genome-wide association study; porcine reproductive and respiratory syndrome.

Figure 1

Viremia following PRRSV infection. Viremia was measured by RT-PCR of viral RNA using a commercial diagnostic PRRSV assay. For the purpose of standardization, the results were reported as number of PRRSV templates per 50 ul PCR reaction. Results are shown for those pigs in a single 200 pig trial that possessed data for all days.

Figure 2

Weight gain during PRRSV infection. Panel (A) shows the weight gain for individual infected pigs for 42 days. Panel (B) shows the weight distribution at 42 days after infection for the same pigs in panel (A). Black squares represent non-infected reference pigs.

Figure 3

Virus load versus weight gain. The figure shows results for a single trial. The virus load was calculated as the area under the curve for viremia over the first 21 days for each pig as described in Figure 1. Average daily gain was calculated as the weight at 42 days after infection minus the weight on the day of virus challenge divided by 42 days. Key: Hv, high virus load; Lv, low virus load; Hg, high weight gain; Lg, low weight gain. Virus load for each pig was determined by calculating the area under the curve for the first 21 days after infection.