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

Abstract

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.

Relationships of CD163 and CD169 positive cell numbers in the endometrium and fetal placenta with type 2 PRRSV RNA concentration in fetal thymus

“…These results provide improved insights into the events occurring at the maternal–fetal interface during type 2 PRRSV infection and help clarify the pathogenesis of PRRSV transplacental infection and induced reproductive failure. Previous studies [ 28 , 29 ] as well as our observations in a related histopathology study of type 2 PRRSV infection in pregnant gilts [ 24 ] confirmed that type 2 PRRSV infection causes significant microscopic lesions in the uterus and fetal placenta at the maternal–fetal interface. Consequently, we hypothesized that in addition to CD169 and CD163 + cells, PRRSV in utero infection is influenced by other factors involving epithelial cells of MFI and areolae.…”

“…Three routes of transplacental spread of PRRSV have been discussed in the literature [ 23 ], such as direct spread from infected macrophages to epithelial cells of uterus and fetal placenta, spread of free PRRS viral particles, and migration of infected macrophages from mother to the fetus. Results of our histopathological evaluation of type 2 PRRSV infection in pregnant gilts in the third trimester of pregnancy confirmed marked inflammatory changes affecting the maternal–fetal chorionic interdigitation areas [ 24 ] and suggested potential role for inflammatory cells and resident macrophages in PRRSV infection of the fetal placenta and fetus [ 23 ]. In order to further test this hypothesis, we developed two objectives for the present study.…”

Maternal and fetal thyroid dysfunction following porcine reproductive and respiratory syndrome virus2 infection

“…Previous studies evaluating the histopathology in fetal hearts from the pregnant gilt model found heart lesions (mild, focal to multifocal, lymphocytic myocarditis and perivascular cuffing) were rarely observed in the fetal population (3.92% of PRRSV-infected fetuses) but were more prevalent in meconium stained and decomposed fetuses (14.5% and 5.9%, respectively) compared to viable fetuses (1%) providing some evidence that heart is involved in fetal compromise [4]. To further evaluate the impact of hypothyroidism on cardiac function, we investigated a combination of genes associated with contractile activity, response to stress and maturation for extrauterine life, all of which have previously been shown to be altered in the hypothyroid fetus, particularly in thyroidectomy models [35,39,49].…”

“…This rather surprising result may indicate that suppression of the fetal thyroid hormone system confers some benefit during serious viral infection. PRRSV infection has been shown to significantly increase both the occurrence of placental separation [4] and apoptosis [38]. These disruptions would compromise placental efficiency during a period of elevated fetal growth and requirement, creating a transport deficit likely to result in fetal hypoxia.…”

“…Given the inability to completely control or eradicate PRRSV2 though classical methods such as vaccination and biosecurity, there is continued interest in identifying the precise cause of fetal mortality following infection to facilitate development of alternative methods of control and potentially novel therapeutic treatments. With mounting evidence that viral damage to the placenta is not responsible for fetal compromise [4], there is renewed interest in the direct impact of this virus on the fetus and the potential longer-term implications of disruptions in the critical systems and processes that drive development and maturation of surviving fetuses.…”