Abstract
Stimulation of the CD95 (Apo-1/Fas) molecule either by the CD95 ligand or by monoclonal antibodies induces programmed cell death by apoptosis in a variety of cell lines and primary cells. In this study we observed that infection of B lymphoblast and T lymphoblast cell lines with vaccinia virus strain WR and recombinant vaccinia WR constructs, but not strain Copenhagen, rendered cells refractory to CD95-mediated apoptosis. In particular, vaccinia virus infection suppressed anti-CD95 antibody-induced membrane disintegration, apoptotic nuclear morphology of cells, and DNA fragmentation. Inhibition of apoptosis was not mediated by CD95 down-regulation or reduced binding of anti-CD95 antibody to infected cells, and occurred at a time point when cellular metabolism was not yet affected by the lytic vaccinia virus infection. Vaccinia virus (WR)-infected cells were resistant to CD95 ligand–CD95-mediated lysis by CD4+ and CD8+, T lymphocytes. Because cytolysis mediated by CD95 is one of two major mechanisms used by cytotoxic T lymphocytes to kill target cells, inhibition of CD95-mediated apoptosis may constitute a novel immune escape mechanism for this virus. Additionally, this mechanism may contribute to the higher pathogenicity of vaccinia virus strain WR compared with strain Copenhagen.
Keywords: CD95, vaccinia, apoptosis, Apo-1, Fas
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