Selective induction of apoptosis in antigen-presenting cells in mice by Parapoxvirus ovis

Viruses have evolved numerous mechanisms to avoid host immune reactions. Here we report a mechanism by which Parapoxvirus ovis (PPVO) interferes with antigen presentation. PPVO (orf virus) causes orf, an acute skin disease of sheep and goats worldwide. Importantly, PPVO can repeatedly infect its host in spite of a vigorous inflammatory and host immune response to the infection. We demonstrate in a mouse system that PPVO induces apoptosis in a significant number of antigen-presenting cells after intraperitoneal injection using the CD95 pathway, thus preventing a primary T-cell response. We also show that PPVO induces a compensatory activation of the immune system. Our results may help to explain the phenomenon that natural PPVO infections in sheep occur repeatedly even after short intervals. They also suggest that the combination of immunosuppressive and immunostimulatory mechanisms is an effective survival strategy that might be used in other viruses as well.