Induction of interferon-gamma and downstream pathways during establishment of fetal persistent infection with bovine viral diarrhea virus

Smirnova, Natalia P., Webb, Brett T., McGill, Jodi L., Schaut, Robert G., Bielefeldt-Ohmann, Helle, Van Campen, Hana, Sacco, Randy E. and Hansen, Thomas R. (2014) Induction of interferon-gamma and downstream pathways during establishment of fetal persistent infection with bovine viral diarrhea virus. Virus Research, 183 95-106. doi:10.1016/j.virusres.2014.02.002

Author Smirnova, Natalia P.
Webb, Brett T.
McGill, Jodi L.
Schaut, Robert G.
Bielefeldt-Ohmann, Helle
Van Campen, Hana
Sacco, Randy E.
Hansen, Thomas R.
Title Induction of interferon-gamma and downstream pathways during establishment of fetal persistent infection with bovine viral diarrhea virus
Journal name Virus Research   Check publisher's open access policy
ISSN 1872-7492
Publication date 2014-04-21
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.virusres.2014.02.002
Volume 183
Start page 95
End page 106
Total pages 12
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Formatted abstract
Development of transplacental infection depends on the ability of the virus to cross the placenta and replicate within the fetus while counteracting maternal and fetal immune responses. Unfortunately, little is known about this complex process. Non-cytopathic (ncp) strains of bovine viral diarrhea virus (BVDV), a pestivirus in the Flaviviridae family, cause persistent infection in early gestational fetuses (<150 days; persistently infected, PI), but are cleared by immunocompetent animals and late gestational fetuses (>150 days; transiently infected, TI). Evasion of innate immune response and development of immunotolerance to ncp BVDV have been suggested as possible mechanisms for the establishment of the persistent infection. Previously we have observed a robust temporal induction of interferon (IFN) type I (innate immune response) and upregulation of IFN stimulated genes (ISGs) in BVDV TI fetuses. Modest chronic upregulation of ISGs in PI fetuses and calves reflects a stimulated innate immune response during persistent BVDV infection. We hypothesized that establishing persistent fetal BVDV infection is also accompanied by the induction of IFN-gamma (IFN-γ). The aims of the present study were to determine IFN-γ concentration in blood and amniotic fluid from control, TI and PI fetuses during BVDV infection and analyze induction of the IFN-γ downstream pathways in fetal lymphoid tissues. Two experiments with in vivo BVDV infections were completed. In Experiment 1, pregnant heifers were infected with ncp BVDV type 2 on day 75 or 175 of gestation or kept naïve to generate PI, TI and control fetuses, respectively. Fetuses were collected by Cesarean section on day 190. In Experiment 2, fetuses were collected on days 82, 89, 97, 192 and 245 following infection of pregnant heifers on day 75 of gestation. The results were consistent with the hypothesis that ncp BVDV infection induces IFN-γ secretion during acute infection in both TI and PI fetuses and that lymphoid tissues such as spleen, liver and thymus, serve both as possible sources of IFN-γ and target organs for its effects. Notably, induction of IFN-γ coincides with a decrease in BVDV RNA concentrations in PI fetal blood and tissues. This is the first report indicating the possible presence of an adaptive immune response in persistent BVDV infections, which may be contributing to the observed reduction of viremia in PI fetuses.
Keyword Bovine viral diarrhea virus
Immune response
Persistent infection
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
School of Veterinary Science Publications
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