Location: Virus and Prion ResearchTitle: Pathogenesis of HP-PRRSV in gnotobiotic pigs) Author
|Kehrli Jr, Marcus|
Submitted to: Porcine Reproductive and Respiratory Syndrome International Symposium
Publication Type: Abstract Only
Publication Acceptance Date: 10/15/2012
Publication Date: 11/29/2012
Citation: Lager, K.M., Faaberg, K.S., Brockmeier, S.L., Miller, L.C., Kappes, M.A., Spear, A., Kehrli, Jr., M.E. 2012. Pathogenesis of HP-PRRSV in gnotobiotic pigs. 2012 International PRRS Symposium. p. 92. Interpretive Summary:
Technical Abstract: Introduction: Porcine high fever disease (PHFD) was first described in China as an acute onset of high morbidity and mortality in growing pigs. Although a number of bacterial and viral pathogens were isolated from these cases, porcine reproductive and respiratory syndrome virus (PRRSV) was consistently detected leading to the assumption that PRRSV was the cause. PHFD was reproduced with virus derived from an infectious clone of the PHFD JX143 PRRSV isolate resulting in this lineage of virus being called highly pathogenic PRRSV (HP-PRRSV). In previous studies, virus rescued from a full-length clone of a 2006 Chinese HP-PRRSV (JXwn06) induced severe disease in conventionally-raised pigs leading to 100% mortality in 4-week-old pigs. In contrast, pigs given VR-2332 challenge virus were much less affected with a mild fever and no mortality. A variety of respiratory bacterial pathogens and opportunists were isolated from the HP-PRRSV infected group. Based on clinical signs, lesions, and bacterial loads in previous studies, we hypothesized HP-PRRSV has a potent immunomodulating capacity that negatively affects the pig’s homeostasis allowing the onset of secondary bacterial disease which contributes significantly to the clinical disease. A study using germ-free pigs housed in sterile isolators was conducted to evaluate the pathogenic potential of HP-PRRSV in the absence of bacteria. Methods: Germ-free pigs were surgically derived and housed in sterile isolators. At 15 days-of-age 12 pigs were inoculated with about 1000 CCID50 virus derived from the JXwn06 HP-PRRSV isolate, and 5 pigs were left as controls. Pigs were scheduled to be bled on 0, 4, 7, 11, and 14 days-post-challenge (dpc). Periodic rectal swabs collected from the pigs were used to monitor bacterial-free status. At necropsy, tissues were collected for histopathology. Virus load was determined by testing ante-mortem plasma samples and the bronchoalveolar lavage collected at necropsy for virus titer. Results: Control pigs remained normal throughout the study. Most virus-challenged pigs began developing anorexia, fever, and listlessness 2 dpc; the clinical signs were variable and intermittent for the next 2-3 days as the pigs became more affected. By 6 dpc some pigs were severely affected and a seizure was observed in 2 pigs. Several pigs had developed a dark stool and one pig passed frank blood. A pig was euthanized the evening of 6 dpc and within 24 hours 7 more pigs were either found dead or were euthanized. The remaining 4 pigs had succumbed by 12 dpc. Gross lesions in most pigs consisted of a mild pneumonia and petechial hemorrhages to varying degrees in the cortex of the kidney. In addition, about half of the pigs had a hemorrhagic enteritis and swollen kidneys. Cutaneous petechial hemorrhages were noted in two pigs. Histopathology results are pending. One isolator containing 4 pigs became contaminated with bacteria, although the GI tract became colonized in each pig, no sepsis was found (bacterial identification pending). Virus loads were similar to previous conventional pig studies. Conclusion: The objective of this pig study was to evaluate the pathogenicity of the JXwn06 HP-PRRSV in the absence of bacteria. The virus induced a fatal disease in the gnotobiotic pig model beginning about 6 dpc. Interestingly, this is about the time when the onset of mortality is observed in the conventional pig model. Moreover, the clinical disease in the one contaminated isolator was similar to what was seen in the other 2 isolators suggesting the bacterial infection did not potentiate the disease. Additional studies will be necessary to understand the putative synergy between HP-PRRSV and bacteria.