Porcine reproductive and respiratory syndrome (PRRS) continues to be an important emerging disease of swine. This disease is disruptive to swine operations as the result of reproductive problems in the breeding herd; premature farrowing of late term fetuses; and severe respiratory problems in nursery pigs.4 Current field observations and diagnostic laboratory data suggest that the acute "reproductive disease storms" commonly observed in field outbreaks of PRRS in 1987-89 are now less frequent. Currently, an acute and chronic respiratory form of PRRS, which appears to be endemic in the United States and Europe, appears to be the most common form of the disease.

The major breakthrough in resolving the "mystery" of PRRS occurred in 1991 to 1992, when investigators in The Netherlands8 and the United States1,2 reported the isolation of a small, single-stranded RNA virus as the cause of PRRS. Both the Netherlands (Lelystad virus) and the U.S. isolates (VR-2332) were subsequently classified as arteriviruses based on morphologic, physico-chemical and genetic properties.1,3,5,6,8 Now that PRRS and its causative agent are no longer a mystery, there have been an increasing number of studies on the: molecular properties of the virus, epidemiology, pathogenesis, immunity, and diagnosis. One of the most significant achievements in the past year, has been the sequencing of the genome of the U.S. isolate of PRRS virus by Dr. Mike Murtaugh and colleagues at the University of Minnesota.6

Our recent research efforts have focused on defining the pathogenesis of the VR-2332 isolate of PRRS virus and a summary of our results-to-date are presented in this report.

To determine how the PRRS virus enters the respiratory tract of the pig and causes disease.

Understanding the pathogenesis of PRRS may provide information on: shedding patterns of the virus; specific tissues targeted by the virus; mechanisms on how the virus damages tissues and causes disease; and methods to effectively prevent, control or moderate the effects of the PRRS virus.

Approach

Three-day-old gnotobiotic pigs were intranasally inoculated with the VR-2332 isolate of PRRS virus and euthanized at 12 hours, 1, 2, 3, 5, 7, 14, and 21 days post-inoculation (PI). Various tissues were then assayed for PRRS virus and examined for gross and microscopic lesions.

We were unable to identify the initial site of viral replication, but high titers of PRRS virus were detected in the blood as early as 12 hours PI. Virus was also isolated from the lung of some pigs at 12 hours PI. However, in most cases, virus was detected in the blood prior to being isolated from other tissues. Virus was most frequently isolated at all sampling times from mandibular lymph node, tonsil, spleen, thymus, nasal turbinate and heart of inoculated pigs. All inoculated pigs also seroconverted by 14 days PI.

Gross lesions were occasionally observed on the lungs of inoculated pigs. Microscopic lesions were consistently observed in the lung, lymph nodes, heart and blood vessels of the PRRS virus-inoculated pigs. Lung lesions were most prominent beginning at 3 days PI and persisted throughout the 21 day PI experimental period. Microscopic lesions in the lymph nodes and blood vessels varied in distribution and severity and were most prominent in pigs euthanized at 14 and 21 days PI. All inoculated pigs had heart lesions at 21 days PI. The lesions were similar to those previously described.2,7 The lymph nodes in many of the PRRS virus-inoculated pigs are two to four times the diameter of those from mock-inoculated pigs. These enlarged lymph nodes appear to be a prominent lesion in pigs born live to PRRS virus infected sows.

On the basis of these results, we present a proposed model for the pathogenesis of PRRS virus (see figure on last page). In this model, we postulate that the multi-systemic effects of PRRS (virus spread to multiple tissues) is the result of the early viremia. Virus most likely reaches the main target, alveolar macrophages, via blood contamination. In addition, many of the clinical signs of PRRS such as periorbital and scrotal edema can be explained by the viral damage to blood vessels. Respiratory distress is the direct result of replication in alveolar macrophages and blood vessels resulting in the interstitial pneumonia. The increase in secondary bacterial infections, especially respiratory infections, are most likely due to viral damage to alveolar macrophages.

Most, if not all, the effects of the PRRS virus are mediated as a direct result of blood borne virus. From a practical standpoint, viral diseases with a viremia (virus in the blood) are most amendable to control by live-attenuated or killed vaccines. Vaccines, which induce an immune response capable of reducing or eliminating the PRRS virus in the blood, should theoretically moderate PRRS viral infections. The key to a successful PRRS vaccine will be to find either an attenuated strain of PRRS virus or a subunit of the virus, which induces the proper immune response that will neutralize most strains of the PRRS virus.

Funding for these studies was provided by the National Pork Producers Council, South Dakota Pork Producers Council, South Dakota and Minnesota Agricultural Experiment Stations, and the USDA National Research Initiative Competitive Grant # 92-03683.

Figure 1. Proposed Pathogenisis Model for VR-2332 Isolate of PRRS Virus

1. Benfield, DA, E Nelson, JE Collins, L Harris, SM Goyal, D Robison, WT Christianson, RB Morrison, D Gorcyca, D Chladek. 1992. Characterization of swine infertility and respiratory syndrome (SIRS) virus (Isolate ATCC VR-2332). J Vet Diag Invest 4:127-133.

2. Collins JE, DA Benfield, WT Christianson, L Harris, JC Hennings, DP Shaw, SM Goyal, D Gorcyca, D Chladek, S McCullough, RB Morrison, HS Joo. 1992. Isolation of swine infertility and respiratory syndrome virus (Isolate ATCC VR-2332) in north america and experimental reproduction of the disease in gnotobiotic pigs. J Vet Diagn Invest 4:117-126.

3. Conzelman, KK, N Visser, P Van woensel, and HJ Thiel. 1993. Molecular characterization of porcine reproductive and respiratory syndrome virus, a member of the arterivirus group. Virology 193:329-339.

4. Loula, T. 1991. Mystery pig disease. Agri-Practice 12:23-34.

5. Meulenberg, JJM, MM Hulst, EJ de Meijer, PLJM Moonen, A den Besten, EP de Kluyver, G Wensvoort, RJM Moormann. 1993. Lelystad virus, the causative agent of porcine epidemic abortion and respiratory syndrome (PEARS), is related to LDV and EAV. Virology 192:62-72.

6. Murtaugh, MP, M Elam, L Kakach. 1993. Comparison of the structural protein coding sequence of Lelystad and VR-2332 strains of the PRRS virus. IXth Int Cong Virology, Glasgow, Scotland. August 8-13, 1993. Abstract p. 132.

7. Rossow, KD, EM Bautista, SM Goyal, TW Molitor, MP Murtaugh, RB Morrison, DA Benfield, JE Collins. 1994. Experimental porcine reproductive and respiratory syndrome virus infection in one-, four-, and 10-week-old pigs. J Vet Diagn Invest 6:3-12.

8. Wensvoort G, C Terpstra, JMA Pol, EA ter Laak, M Bloemrad, EP deKluyer, C Kragten, L van Buiten, A den Besten, F Wagenaar, JM Broekhuijsen, PLJM Moonen, T Zetstra, EA de Boer, HJ Tibben, MF de Jong, P van’t Veld, GJR Groenland, JA van Gennep, MTh Voets, JHM Verheijden, J Braamskamp. 1991. Mystery swine disease in the Netherlands: the isolation of Lelystad virus. The Vet Quarterly 13:121-130.