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.
BVDV can interrupt pregnancy recognition and evade host detection in the uterine endometrium by downregulation of interferon signaling pathways