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.