Identification of peripheral blood mononuclear cells targeted by Ovine herpesvirus-2 in sheep.

Sheep-associated malignant catarrhal fever (MCF), caused by Ovine herpesvirus 2 (OvHV-2), is usually a fatal disease of various ruminants and swine. In contrast, natural OvHV-2 infection in sheep, which are the main OvHV-2 reservoir, proceeds without any clinical symptoms. Since the range of targeted cells may be important for pathogenesis, we wanted to analyze the natural range of peripheral mononuclear blood cells (PBMC) targeted by OvHV-2. To this end, OvHV-2-free sheep were exposed to natural infection and blood samples were taken at intervals. Four different PBMC subpopulations were purified by fluorescence activated cell sorting (FACS) before being subjected to analysis for OvHV-2-DNA. After an incubation period of between 11 and 12 weeks, all exposed sheep became positive for OvHV-2. In most sheep, a first peak of OvHV-2-DNA was identified in the CD2 and CD4 double positive subpopulation. However, with time, the highest load of OvHV-2-DNA shifted to the CD2-positive and CD4-negative T-cells. Furthermore, low amounts of OvHV-2-DNA were occasionally detected also in the fractions that represented either CD14-positive monocytes or triple negative cells (CD2(-)/CD4(-)/CD14(-)). We conclude from these experiments that OvHV-2 has a similar host cellular range in sheep and cattle, respectively. Our results may be relevant in the context of comparative analysis of OvHV-2 pathogenesis in animal species that are susceptible to MCF.

The long-term but not the short-term antiviral effect of IFN-alpha depends on Flt3 ligand and pDC.

The cooperation between IFN-alpha/beta and FL, the ligand of Fms-like tyrosine kinase 3 (Flt3), plays an important role in the defense against herpes simplex virus type 1 (HSV-1) in neonates. Treatment of neonatal mice with recombinant IFN-alpha has a short-term, FL-independent and a long-term, FL-dependent protective effect against HSV-1. In mice lacking FL, neonatal resistance against HSV-1 is very low and DC numbers in the spleen are reduced. The treatment of these mice with rIFN-alpha at day 6 resulted in an increased resistance against infection with HSV-1 at day 7. In C57BL/6 mice, treatment with rIFN-alpha at birth induced both FL and plasmacytoid DC (pDC), resulting in enhanced resistance against HSV-1 at day 7. In contrast, in mice lacking FL, IFN-alpha treatment at birth did not influence the splenic cell composition and had no effect on viral protection. The transfer of pDC to mice lacking FL enhanced viral resistance. Therefore, the induction and function of pDC, normally controlled by IFN-alpha/beta and FL, are decisive for viral resistance in neonatal mice.