Bovine viral diarrhea virus (BVDV) can evade host detection by downregulation of interferon signaling pathways. Infection of cows with noncytopathic (ncp) BVDV can cause early embryonic mortality. Upregulation of type I interferon stimulated genes (ISGs) by blastocyst-secreted interferon tau (IFNT) is a crucial component of the maternal recognition of pregnancy (MRP) in ruminants. This study investigated the potential of acute BVDV infection to disrupt MRP by modulating endometrial ISG expression. Endometrial cells from 10 BVDV-free cows were cultured and treated with 0 or 100 ng/ml IFNT for 24 h in the absence or presence of ncpBVDV infection to yield four treatment groups: CONT, ncpBVDV, IFNT, or ncpBVDV+IFNT. ncpBVDV infection alone only upregulated TRIM56, but reduced mRNA expression of ISG15, MX2, BST2, and the proinflammatory cytokine IL1B. As anticipated, IFNT treatment alone significantly increased expression of all 17 ISGs tested. In contrast to the limited effect of ncpBVDV alone, the virus markedly inhibited IFNT-stimulated expression of 15 ISGs tested (ISG15, HERC5, USP18, DDX58, IFIH1, IFIT1, IFIT3, BST2, MX1, MX2, RSAD2, OAS1Y, SAMD9, GBP4, and PLAC8), together with ISG15 secreted protein. Only TRIM56 and IFI27 expression was unaltered. IL1B expression was reduced by the combined treatment. These results indicate that acute ncpBVDV infection may decrease uterine immunity and lead to MRP failure through inhibition of IFNT-stimulated endometrial ISG production. This in turn could reduce fertility and predispose cows to uterine disease, while evasion of the normal uterine immune response by ncpBVDV may contribute to maintenance and spreading of this economically important disease.

Embryonic mortality in cows is at least in part caused by failure of pregnancy recognition (PR). Evidence has shown that bovine viral diarrhoea virus (BVDV) infection can disrupt pregnancy. Prostaglandins (PG) play important roles in many reproductive processes, such as implantation. The aim of this study was to investigate the effect of BVDV infection on uterine PG production and PR using an in vitro PR model. Bovine uterine endometrial cells isolated from ten BVDV-free cows were cultured and treated with 0 or 100 ng/mL interferon-τ (IFNT) in the absence or presence of non-cytopathic BVDV (ncpBVDV). PGF 2α and PGE 2 concentrations in the spent medium were measured using radioimmunoassays, and in the treated cells expression of the genes associated with PG production and signalling was quantified using qPCR. The results showed that the IFNT challenge significantly stimulated PTGS1 and PTGER3 mRNA expression and PGE 2 production; however, these stimulatory effects were neutralised in the presence of ncpBVDV infection. ncpBVDV infection significantly increased PTGS1 and mPGES1 mRNA expression and decreased AKR1B1 expression, leading to increased PGE 2 and decreased PGF 2α concentrations and an increased PGE 2 :PGF 2α ratio. The other tested genes, including PGR, ESR1, OXTR, PTGS2, PTGER2 and PTGFR, were not significantly altered by IFNT, ncpBVDV or their combination. Our study suggests that BVDV infection may impair PR by (1) inhibiting the effect of IFNT on uterine PG production and (2) inducing an endocrine switch of PG production from PGF 2α to PGE 2 to decrease uterine immunity, thereby predisposing the animals to uterine disease.Reproduction (2016) 151 605-614

Optic neuritis (ON) is a recognized condition, yet factors influencing recovery of vision are currently unknown. The purpose of this study was to identify prognostic factors for recovery of vision in canine ON of unknown etiology. Clinical databases of three referral hospitals were searched for dogs with presumptive ON based on clinicopathologic, MRI/CT, and fundoscopic findings. Twenty-six dogs diagnosed with presumptive ON of unknown etiology, isolated (I-ON) and MUE-associated (MUE-ON), were included in the study. Their medical records were reviewed retrospectively, and the association of complete recovery of vision with signalment, clinicopathologic findings, and treatment was investigated. Datasets were tested for normality using the D'Agostino and Shapiro-Wilk tests. Individual datasets were compared using the Chi-squared test, Fisher's exact test, and the Mann-Whitney U-test. For multiple comparisons with parametric datasets, the one-way analysis of variance (ANOVA) was performed, and for non-parametric datasets, the Kruskal-Wallis test was performed to test for independence. For all data, averages are expressed as median with interquartile range and significance set at p < 0.05. Twenty-six dogs met the inclusion criteria. Median follow-up was 230 days (range 21–1901 days, mean 496 days). Six dogs (23%) achieved complete recovery and 20 dogs (77%) incomplete or no recovery of vision. The presence of a reactive pupillary light reflex (p = 0.013), the absence of fundoscopic lesions (p = 0.0006), a younger age (p = 0.038), and a lower cerebrospinal fluid (CSF) total nucleated cell count (TNCC) (p = 0.022) were statistically associated with complete recovery of vision. Dogs with I-ON were significantly younger (p = 0.046) and had lower CSF TNCC (p = 0.030) compared to the MUE-ON group. This study identified prognostic factors that may influence complete recovery of vision in dogs with ON. A larger cohort of dogs is required to determine whether these findings are robust and whether additional parameters aid accurate prognosis for recovery of vision in canine ON.