Pathogenesis and prevention of placental and transplacental porcine reproductive and respiratory syndrome virus infection

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV)-induced reproductive problems are characterized by embryonic death, late-term abortions, early farrowing and increase in number of dead and mummified fetuses, and weak-born piglets. The virus recovery from fetal tissues illustrates transplacental infection, but despite many studies on the subject, the means by which PRRSV spreads from mother to fetus and the exact pathophysiological basis of the virus-induced reproductive failure remain unexplained. Recent findings from our group indicate that the endometrium and placenta are involved in the PRRSV passage from mother to fetus and that virus replication in the endometrial/placental tissues can be the actual reason for fetal death. The main purpose of this review is to clarify the role that PRRSV replication and PRRSV-induced changes in the endometrium/placenta play in the pathogenesis of PRRSV-induced reproductive failure in pregnant sows. In addition, strategies to control placental and transplacental PRRSV infection are discussed.

Figure 1

Porcine placental barrier and conceptus. Representations of the placental barrier in swine (A) and conceptus within the uterine horn (B).

Figure 2

Events during PRRSV infection in the maternal-fetal interface in sows intranasally inoculated at 90 days of gestation. 1. Maternal blood vessel. 2. Endometrial connective tissue. 3. Uterine epithelium. 4. Trophoblast. 5. Fetal placental mesenchyme. 6. Fetal blood vessel. (A) During viremia PRRSV attaches and probably enters and replicates in susceptible monocytes adhering to the endothelial cells of the endometrial vessels. Extravasation of the PRRSV-bearing monocytes from maternal blood to the endometrium. (B) PRRSV replicates in the endometrial macrophages. PRRSV causes apoptosis in infected and surrounding cells during replication within the endometrium. PRRSV crosses the uterine epithelium and trophoblast, most probably in association with maternal macrophages. (C) Focal, highly efficient PRRSV replication in the fetal placental macrophages. PRRSV reaches fetal internal organs most likely through the umbilical circulation. PRRSV causes apoptosis in infected and surrounding cells during replication in the placenta. (D) Maternal immunity (most probably CD8⁺ endometrial NK cells) suppresses PRRSV replication within the endometrium. Focal, highly efficient PRRSV replication in the placenta. (E) Focal detachment of the trophoblast from the uterine epithelium and focal degeneration of the placenta, at the places of virus replication and probably in the adjacent sites. (F) Multifocal degeneration and finally full degeneration of the placenta, at the places of virus replication, and probably in the adjacent sites.

Figure 3

PRRSV-positive macrophages in the endometrium (A) and placenta (B). PRRSV-positive macrophages (arrowed) in close proximity to the uterine (maternal) epithelium (mep) and fetal trophoblast cells (tr). MSF: maternal secondary fold.