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 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 refractor to CD95-medicated 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.
Heinkelein
M
M
Institute for Virology and Immunobiology, University of Würzburg, Germany.
Pilz
S
S
Jassoy
C
C
D017209:Apoptosis; D001666:Binding Sites, Antibody; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000276:immunology / Q000473:pathology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004249:DNA Damage / Q000276:immunology; D015536:Down-Regulation; D006801:Humans; D007113:Immunity, Innate; D007165:Immunosuppression Therapy; D011506:Proteins / Q000378:metabolism; D013045:Species Specificity; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology*
D011506:Proteins; D019014:fas Receptor