Type 2 porcine reproductive and respiratory syndrome virus infection increases apoptosis at the maternal-fetal interface in late gestation pregnant gilts

Abstract

The pathogenesis of fetal death associated with porcine reproductive and respiratory syndrome (PRRS) is hypothesized to be a consequence of PRRS virus-induced apoptosis at the maternal-fetal interface (MFI). The objectives of this study were to evaluate distribution and degree of apoptosis in the uterine and fetal placental tissues during the experimental type 2 PRRS virus (PRRSV) infection and determine associations between apoptosis at the MFI, PRRSV RNA concentration and antigen staining intensity, PRRSV-induced microscopic lesions, and fetal preservation status. A total of 114 naïve, high-health pregnant gilts were inoculated with type 2 PRRSV on gestation day 85±1 with euthanasia 21 days later; 19 sham-inoculated gilts served as controls. Two hundred and fifty samples of uterine tissue with fetal placenta were selected based on negative, low PRRSV RNA, and high PRRSV RNA concentration (0, < or > 2.7 log10 copies/mg, respectively). TUNEL assay was used to detect apoptosis in the endometrium and at the MFI. PRRSV RNA concentration and numbers of PRRSV immunopositive cells in uterine and placental tissue were positively associated with the severity of apoptosis in the endometrium and the MFI (P<0.001, P<0.05 and P<0.001, respectively). The number of TUNEL positive cells at the MFI was also positively associated with the severity (P<0.001) of vasculitis, but not total numbers of inflammatory cells in the endometrium. Increased numbers of TUNEL positive cells at the MFI were associated with PRRSV load in the fetal thymus, and greater odds of meconium staining of the fetus at 21 days post infection (P<0.001 for both). These findings suggest an important role of apoptosis in the pathogenesis of uterine epithelial and trophoblastic cell death at the MFI. Moreover, apoptosis at the MFI is significantly associated with fetal demise during in utero type 2 PRRSV infection.

Differential responses in placenta and fetal thymus at 12 days post infection elucidate mechanisms of viral level and fetal compromise following PRRSV2 infection

“…Across all groups of virus positive fetuses in the placenta, we see a strong activation and enrichment of genes in the Apoptosis and Ubiquitination Pathways. PRRSV causes apoptosis in the maternal uterine epithelium and fetal trophoblast epithelium as well as surrounding cells in late gestation [ 6 , 44 ].…”

A comparison of the severity of reproductive failure between single and dual infection with porcine reproductive and respiratory syndrome virus (PRRSV)-1 and PRRSV-2 in late-term pregnancy gilts

“…Although the concentration of PRRSV viremia in the dam is of little importance for the reproductive outcomes (Harding et al., ; Ladinig et al., ), maternal viremia plays a critical role in transplacental infection of foetuses in pregnant gilts (Christianson et al., ; Kranker, Nielsen, Bille‐Hansen, & Botner, ; Karniychuk & Nauwynck, ). Once PRRSV infects the uterine and foetal placental tissues through maternal viremia, it can induce apoptosis at the maternal–foetal interface (Karniychuk & Nauwynck, 2013; Novakovic, Harding, Al‐Dissl, & Detmer, ) spreading to foetal tissues and ultimately lead to foetal death (Ladinig et al., ). The presence of PRRSV in foetuses, particularly at high levels in the thymus, contributes to foetal death (Ladinig et al., ).…”

Complete Genome Sequence of a Novel Subgenotype of Porcine Reproductive and Respiratory Syndrome Virus Strain JX/CH/2016, Isolated in Jiangxi, China

“…Porcine reproductive and respiratory syndrome virus (PRRSV), the causative agent of porcine reproductive and respiratory syndrome (PRRS), is a small, enveloped, positive-sense, single-stranded RNA virus that belongs to the Arteriviridae family ( 1 , 2 ). According to its genetic and antigenic characteristics, PRRSV has been divided into two major genotypes, the European type (Lelystad virus [LV] is the representative prototype) and the North American type (VR-2332 virus is the prototype) ( 3 – 5 ). The epidemiology of PRRSV in China is complex.…”