M. Heinkelein et al., INHIBITION OF CD95 (FAS APO1)-MEDIATED APOPTOSIS BY VACCINIA VIRUS WR/, Clinical and experimental immunology, 103(1), 1996, pp. 8-14
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.