PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS: PATHOLOGICAL EFFECTS ON THE PLACENTA AND TRANSPLACENTAL TRANSMISSION

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is a disease with important economic impacts in the swine industry. Despite its importance, key events of its pathophysiology and transplacental transfer of the virus are still unknown. The objectives in our projects were to evaluate relevant factors in the physiology of placental tissues that can be affected by infection with PRRSV and the possible route that the virus uses to cross the transplacental barrier. For these evaluations, thirty-one pregnant gilts inoculated with a type 2 PRRSV (PRRSV2) at gestation day 86±0.4, and seven sham-inoculated pregnant gilts were used. All gilts were euthanized at 12 days post-inoculation. Different phenotypic fetal groups were evaluated including uninfected (UNIF), placenta only infected (PLCO), high viral load viable (HVL-VIA), and HVL-meconium stained (MEC) from PRRSV-infected gilts, as well from sham-inoculated (CON) gilts. Finally, potential factors related to PRRSV2 localization, including the severity of inflammation in endometrium and placenta, and intrauterine growth restriction (IUGR) were assessed. Angiogenesis and cell proliferation in placental tissues are fundamental physiological events during pregnancy whereas PRRSV2 infections alter placental tissues through inflammatory and apoptotic pathways. Our first hypothesis was that PRRSV2 can alter these two physiological processes which can lead to compromised fetal development and survival. Angiogenesis and cell proliferation in the porcine maternal fetal interface (MFI) were determined through the detection of vascular endothelial growth factor (VEGF) and Ki-67, respectively in the porcine maternal fetal interface (MFI). VEGF immunostaining in the uterine submucosa was significantly lower in MEC compared to UNIF and HVL-VIA groups. Significantly greater Ki67 immunostaining was detected in the trophoblasts of CON fetuses versus all other groups, and in uterine epithelium of CON and UNIF fetuses versus HVL-VIA and MEC. These results suggest that fetal resilience may be related to greater cell proliferation in uterine epithelium, and fetal compromise with reduced uterine submucosal angiogenesis, except in intra-uterine growth retarded fetus (IUGR) fetuses in which inherently lower submucosal angiogenesis may be protective against PRRSV2 infection. In addition, we evaluated specialized structures in the placenta called areolae. These structures have high absorptive and substance transport capacity that facilitate embryonic development. The aim of this study was to characterize the localization of PRRSV2 in and adjacent to areolae. Our second hypothesis was that transplacental transmission might occur through placental areolae. Presence of PRRSV2 and CD163+ macrophages were determined using immunofluorescence in cryosections of maternal-fetal interface (MFI) with and without areolae. In the maternal, fetal and cavity of areolar regions, PRRSV2 particles were found both independently and in co-localization with CD163+ macrophages. These results suggest that transplacental transmission of PRRSV2 may occur through the areolae, either as non-cell associated or in association with infected CD163 macrophages.