Novel insights into host responses and the reproductive pathophysiology of type 2 porcine reproductive and respiratory syndrome (PRRS)

Authors: HARDING, JCS - University Of Saskatchewan; LADININIG, A. - University Of Veterinary Medicine; NOVAKOVIC, PREDRAG - University Of Saskatchewan; DETMER, SE - University Of Saskatchewan; WILKINSON, JAMIE - University Of Alberta; YANG, TIANFU - University Of Alberta; Lunney, Joan; PLASTOW, G - University Of Alberta

Submitted to: Veterinary Microbiology
Publication Type: Review Article
Publication Acceptance Date: 2/27/2017
Publication Date: 3/2/2017
Citation: Harding, J., Ladininig, A., Novakovic, P., Detmer, S., Wilkinson, J., Yang, T., Lunney, J.K., Plastow, G. 2017. Novel insights into host responses and the reproductive pathophysiology of type 2 porcine reproductive and respiratory syndrome (PRRS). Veterinary Microbiology. 209: 114-123. 10.1016/j.vetmic.2017.02.019.
DOI: https://doi.org/10.1016/j.vetmic.2017.02.019

Interpretive Summary: We performed a large-scale challenge experiment on the pathophysiology of reproductive porcine reproductive and respiratory syndrome virus (PRRSV) infection. Our goal was to understand why not all fetuses in a litter become infected. Third-trimester pregnant gilts were infected with type 2 PRRSV and deep phenotyping and genotyping performed to identify maternal and fetal factors predictive of PRRS severity and resilience. Cell death (apoptosis) in the maternal-fetal interface region was positively related to endometrial vasculitis, viral load in maternal endometrium and fetal thymus, and the odds of a fetus being PRRSV positive. Viral load at the maternal-fetal interface was a strong predictor of viral load in fetal thymus and odds of fetal death. Fetal death and viral load clustered in litters suggesting inter-fetal transmission starting from a limited number of index fetuses in each litter. Factors associated with index fetal infection are unclear, but large fetuses appear to be at greater risk. Disease progression in fetuses was associated with an up-regulation of genes associated with inflammation, innate immunity, and cell death signaling. Twenty-one genomic regions across 10 chromosomes were associated with important traits including fetal viral load, fetal death and viability; this suggests that future selection for reproductive PRRS resilience may be possible.

Technical Abstract: A large-scale challenge experiment using type 2 porcine reproductive and respiratory virus (PRRSV) provided new insights into the pathophysiology of reproductive PRRS in third-trimester pregnant gilts. Deep phenotyping enabled identification of maternal and fetal factors predictive of PRRS severity and resilience. PRRSV infection resulted in a dramatic decrease in all leukocyte subsets by 2 days post inoculation. Apoptosis in the maternal-fetal interface region was positively related to endometrial vasculitis, viral load in endometrium and fetal thymus, and the odds of meconium staining. Viral load at the maternal-fetal interface was also a strong predictor of viral load in fetal thymus and odds of fetal death, however, interferon-alpha suppression, a consequence of PRRSV infection, was associated with decreased odds of fetal death. Although the prevalence of fetal lesions was low, their presence in fetal organs and umbilical cord was associated with fetal compromise. Fetal death and viral load clustered in litters suggesting inter-fetal transmission starting from a limited number of index fetuses. Factors associated with index fetal infection are unclear, but large fetuses appear at greater risk. Disease progression in fetuses was associated with an up-regulation of genes associated with inflammation, innate immunity, and cell death signaling, and down-regulation of genes associated with cell cycle and lymphocyte quality. A number of maternal transcriptomic responses were associated with PRRS resilience including higher basal gene expression correlated with platelet function, interferon and pro-inflammatory responses. Twenty-one genomic regions across 10 chromosomes were associated with important traits including fetal viral load, fetal death and viability suggesting that selection for reproductive PRRS resilience may be possible in the future.