| Abstrakt: |
Interferons (IFN) are cytokines induced in cells by viral infections that provide a first line of defense against other viral infections. These cytokines are derived from a multi-gene family and classified as Type I IFNs (IFN-I; a,b,j) and Type II IFNg. A pregnancy- and ruminant-specific IFN-I called IFNT was discovered in the late 1980's through cDNA sequencing and is the major protein secreted from the expanding ruminant blastocyst. Like other Type I IFNs, IFNT has strong antiviral activity. However, IFNT is not strongly upregulated in response to viral infection. IFNT also is specifically released from trophoblast cells and has unique critical action on the endometrium through inducing IFN stimulated genes (ISGs) and altering the release of prostaglandin F2a, thereby rescuing the corpus luteum (CL) of early pregnancy. In addition, IFNT induces ISGs in peripheral blood mononuclear cells, CL and liver, which confers resistance of the CL to luteolysis and provides a supportive endocrine role for primary paracrine actions in the endometrium. Induction of maternal ISGs in PBMC and other tissues may facilitate rapid upregulation of type I IFN innate immune responses to infection during pregnancy. The impact of maternal bovine viral diarrhea virus (BVDV) infection on IFNs, ISGs and fetal development was examined during pregnancy. Impaired induction of IFN-I and immune tolerance have been cited as critical to establishment of persistent infection (PI) of the fetus with non-cytopathic (ncp) BVDV. Infection of pregnant cows (d75) with ncpBVDV induces a rapid innate immune response (IFN-I and ISGs) that decreases viral replication and leads to the induction of adaptive immune responses that clears the virus in ∼ 3 weeks. Seven to 14 days after maternal inoculation, ncpBVDV crosses the placenta and induces fetal viremia. Activation of fetal ISGs occurs shortly after fetal exposure to the virus and is accompanied by activation of adaptive immune responses mediated by IFN-γ at the peak of fetal viremia (22 days after the maternal infection). The collective actions of the innate and adaptive immune responses causes a significant decrease in fetal viremia, but fails to eliminate the virus. Clarifying the mechanisms of fetal BVDV persistence in the face of activated IFNs will lead to better management tools, detection, biocontainment and antiviral treatments. Cattle may also be selected that are resistant to BVDV and other viral infections. Likewise, a better understanding of IFNT action during early pregnancy may lead to strategies designed to better manage infertility in ruminants. |
