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J. Virol., Jan 1998, 436-441, Vol 72, No. 1
KR Jerome, JF Tait, DM Koelle and L Corey
Many viruses interfere with apoptosis of infected cells, presumably
preventing cellular apoptosis as a direct response to viral infection.
Since cytotoxic T lymphocytes (CTL) induce apoptosis of infected cells as
part of the "lethal hit," inhibition of apoptosis could represent an
effective immune evasion strategy. We report here herpes simplex virus type
1 (HSV-1) interference with CTL-induced apoptosis of infected cells and
show that HSV-1 inhibits the nuclear manifestations of apoptosis but not
the membrane changes. The HL-60 cell line (human promyelocytic leukemia)
undergoes apoptosis in response to many stimuli, including incubation with
ethanol. After HSV-1 infection (strains E115 and 17+), ethanol-treated
cells did not produce oligonucleosomal DNA fragments characteristic of
apoptosis, as assayed by gel electrophoresis and enzyme-linked
immunosorbent assay. Inhibition was detected 2 h after infection and
increased over time. Importantly, HSV-1-infected cells were resistant to
apoptosis induced by antigen-specific CD4+ CTL, despite the fact that CTL
recognition and degranulation in response to infected targets remained
intact. Unlike HSV-1, HSV-2 (strains 333 and HG52) did not inhibit DNA
fragmentation. In contrast to the inhibition of DNA fragmentation by HSV-1,
none of the HSV-1 or -2 strains interfered with the ethanol-induced
exposure of surface phosphatidylserine characteristic of apoptosis, as
determined by annexin V binding. These results demonstrate that genes of
HSV-1 inhibit the nuclear manifestations of apoptosis but not the membrane
manifestations, suggesting that these may be mediated via separate
pathways. They also suggest that HSV-1 inhibition of CTL-induced apoptosis
may be an important mechanism of immune evasion.
Copyright © 1998, American Society for Microbiology
Herpes simplex virus type 1 renders infected cells resistant to cytotoxic T-lymphocyte-induced apoptosis
Department of Laboratory Medicine, University of Washington, Seattle 98195, USA.
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