Pathologic Evaluation of Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection at the Maternal-Fetal Interface of Late Gestation Pregnant Gilts.

The pathogenesis of fetal death caused by porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n = 114) or sham inoculated (n = 19) at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n = 1391). Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both), but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both). The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both). Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection

Variation in fetal outcome, viral load and ORF5 sequence mutations in a large scale study of phenotypic responses to late gestation exposure to type 2 porcine reproductive and respiratory syndrome virus.

In spite of extensive research, the mechanisms of reproductive disease associated with Porcine Reproductive and Respiratory Syndrome virus (PRRSv) are still poorly understood. The objectives of this large scale study were to evaluate associations between viral load and fetal preservation, determine the impact of type 2 PRRSv on fetal weights, and investigate changes in ORF5 PRRSv genome in dams and fetuses during a 21-day period following challenge. At gestation day 85 (±1), 114 gilts were experimentally infected with type 2 PRRSv, while 19 gilts served as reference controls. At necropsy, fetuses were categorized according to their preservation status and tissue samples were collected. PRRSv RNA concentrations were measured in gilt serum collected on days 0, 2, 6, and 21 post-infection, as well as in gilt and fetal tissues collected at termination. Fetal mortality was 41±22.8% in PRRS infected litters. Dead fetuses appeared to cluster in some litters but appeared solitary or random in others. Nine percent of surviving piglets were meconium-stained. PRRSv RNA concentration in fetal thymus, fetal serum and endometrium differed significantly across preservation category and was greatest in tissues of meconium-stained fetuses. This, together with the virtual absence of meconium staining in non-infected litters indicates it is an early pathological condition of reproductive PRRS. Viral load in fetal thymus and in fetal serum was positively associated with viral load in endometrium, suggesting the virus exploits dynamic linkages between individual maternal-fetal compartments. Point mutations in ORF5 sequences from gilts and fetuses were randomly located in 20 positions in ORF5, but neither nucleotide nor amino acid substitutions were associated with fetal preservation. PRRSv infection decreased the weights of viable fetuses by approximately 17%. The considerable variation in gilt and fetal outcomes provides tremendous opportunity for more detailed investigations of potential mechanisms and single nucleotide polymorphisms associated with fetal death

Data from: Pathologic evaluation of type 2 porcine reproductive and respiratory syndrome virus infection at the maternal-fetal interface of late gestation pregnant gilts

The pathogenesis of fetal death caused by reproductive porcine reproductive and respiratory syndrome virus (PRRSV) remains unclear. The objective of this study was to improve our understanding of the pathogenesis by assessing potential relationships between specific histopathological lesions and PRRSV RNA concentration in the fetuses and the maternal-fetal interface. Pregnant gilts were inoculated with PRRSV (n=114) or sham inoculated (n=19) at 85±1 days of gestation. Dams and their litters were humanely euthanized and necropsied 21 days later. PRRSV RNA concentration was measured by qRT-PCR in the maternal-fetal interface and fetal thymus (n=1391). Presence of fetal lesions was positively related to PRRSV RNA concentration in the maternal-fetal interface and fetal thymus (P<0.05 for both), but not to the distribution or severity of vasculitis, or the severity of endometrial inflammation. The presence of fetal and umbilical lesions was associated with greater odds of meconium staining (P<0.05 for both). The distribution and severity of vasculitis in endometrium were not significantly related to PRRSV RNA concentration in maternal-fetal interface or fetal thymus. Endometrial inflammation severity was positively related to distribution and severity of vasculitis in endometrium (P<0.001 for both). Conclusions from this study suggest that type 2 PRRSV infection in pregnant gilts induces significant histopathological lesions at maternal-fetal interface, but they are not associated with presence of PRRSV in the maternal-fetal interface at 21 days post infection. Conversely, fetal pathological lesions are associated with presence of PRRSV in the maternal-fetal interface and fetal thymus, and meconium staining is significantly associated with the presence of both fetal and umbilical lesions observed 21 days post infection

PGM1 PRRS histopathological grading data

Excel File contains histopathological grading data for distribution, and severity of vasculitis, endometrial inflammation score in the uterine tissues associated with 679 fetuses, qRT-PCR PRRS virus RNA concentration values in the uterine tissues and fetal thymuses, number of fetal and umbilical histopathological lesions and fetal preservation status of 679 fetuses. Also file contains explanation of histological grading schemes used for assessment in this study

Relationship between endometrial inflammation and PRRSV RNA concentration (log₁₀/gram) in fetal thymus.

<p>Endometrial inflammation severity is indicated by 4 coloured lines: minimal (green) = inflammatory cells multifocally present in < 10% of the tissue section; mild (blue) = multifocal to coalescing inflammatory cells infiltrate in 10–25% of the tissue; moderate (red) = diffuse inflammatory cell infiltrate in 25–50% of the tissue; severe (black) = inflammatory cells diffusely present in >50% of the tissue section. Results indicate increased viral load in fetal thymus is associated with decreased probability of moderate and severe endometrial inflammation observed at 21 dpi.</p

Numbers of fetal tissues with histopathological lesions in type 2 PRRSV-infected and negative control pregnant gilts inoculated at gestation day 85 (± 1d).

<p>Numbers of fetal tissues with histopathological lesions in type 2 PRRSV-infected and negative control pregnant gilts inoculated at gestation day 85 (± 1d).</p

Relationship between endometrial inflammation and distribution of vasculitis.

<p>Endometrial inflammation severity is indicated by 4 coloured lines: minimal (green) = inflammatory cells multifocally present in < 10% of the tissue section; mild (blue) = multifocal to coalescing inflammatory cells infiltrate in 10–25% of the tissue; moderate (red) = diffuse inflammatory cell infiltrate in 25–50% of the tissue; severe (black) = inflammatory cells diffusely present in >50% of the tissue section. Results indicate the probability of observing severe endometrial inflammation at 21 dpi increases with more extensive vasculitis distribution.</p