title: Novel insights into host responses and reproductive pathophysiology of porcine reproductive and respiratory syndrome caused by PRRSV-2.
abstract: A large challenge experiment using North American porcine reproductive and respiratory virus (PRRSV-2) provided new insights into the pathophysiology of reproductive PRRS. Deep phenotyping of dams and fetuses identified maternal and fetal predictors of PRRS severity and resilience. PRRSV infection resulted in dramatic decreases in all leukocyte subsets by 2days post inoculation. Apoptosis in the interface region was positively related to endometrial vasculitis, viral load in endometrium and fetal thymus, and odds of meconium staining. Viral load at the maternal-fetal interface was a strong predictor of viral load in fetal thymus and odds of fetal death. However, interferon-alpha suppression, a consequence of PRRSV infection, was protective against fetal death. Although the prevalence of fetal lesions was low, their presence in fetal organs and umbilical cord was strongly 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.
authors.affiliation: Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Dr., Saskatoon, Saskatchewan S7N 5B4, Canada. Electronic address: john.harding@usasak.ca.
authors.forename: John C S
authors.initials: JCS
authors.lastname: Harding
authors.affiliation: Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Dr., Saskatoon, Saskatchewan S7N 5B4, Canada. Electronic address: andrea.ladinig@vetmeduni.ac.at.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ladinig
authors.affiliation: Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Dr., Saskatoon, Saskatchewan S7N 5B4, Canada. Electronic address: predrag.novakovic@usask.ca.
authors.forename: Predrag
authors.initials: P
authors.lastname: Novakovic
authors.affiliation: Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Dr., Saskatoon, Saskatchewan S7N 5B4, Canada. Electronic address: susan.detmer@usask.ca.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Detmer
authors.affiliation: Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2P5, Canada. Electronic address: jamie.wilkinson@ualberta.ca.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Wilkinson
authors.affiliation: Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2P5, Canada. Electronic address: tianfu@ualberta.ca.
authors.forename: Tianfu
authors.initials: T
authors.lastname: Yang
authors.affiliation: Animal Parasitic Diseases Laboratory, Beltsville Agricultural Research Center, Agricultural Research Service, U.S. Department of Agriculture, Beltsville, MD, USA. Electronic address: Joan.Lunney@ARS.USDA.GOV.
authors.forename: Joan K
authors.initials: JK
authors.lastname: Lunney
authors.affiliation: Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2P5, Canada. Electronic address: plastow@ualberta.ca.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Plastow
mesh_terms: D000818:Animals; D016678:Genome / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000276:immunology*; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology*; D019316:Porcine respiratory and reproductive syndrome virus / Q000276:immunology; D012641:Selection, Genetic; D013552:Swine / Q000235:genetics
keywords: Apoptosis; Cytokine; Fetal; Genomics; Leukocyte; Maternal-fetal interface; Mortality; Porcine reproductive and respiratory syndrome (PRRS); Reproduction; Resilience; Transcriptomics