INHIBITION OF CD95 (FAS APO1)-MEDIATED APOPTOSIS BY VACCINIA VIRUS WR/

Stimulation of the CD95 (Apo-1/Fas) molecule either by the CD95 ligand or by monoclonal antibodies induces programmed cell death by apoptosi s in a variety of cell lines and primary cells. In this study we obser ved that infection of B lymphoblast and T lymphoblast cell lines with vaccinia virus strain WR and recombinant vaccinia WR constructs, but n ot strain Copenhagen, rendered cells refractory to CD95-mediated apopt osis. In particular, vaccinia Virus infection suppressed anti-CD95 ant ibody-induced membrane disintegration, apoptotic nuclear morphology of cells, and DNA fragmentation. Inhibition of apoptosis was not mediate d 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 v irus (WR)-infected cells were resistant to CD95 ligand-CD95-mediated l ysis by CD4(+) and CD8(+) T lymphocytes. Because cytolysis mediated by CD95 is one of two major mechanisms used by cytotoxic T lymphocytes t o kill target cells, inhibition of CD95-mediated apoptosis may constit ute a novel immune escape mechanism for this virus. Additionally, this mechanism may contribute to the higher pathogenicity of vaccinia viru s strain WR compared with strain Copenhagen.