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J Virol, August 1998, p. 6851-6857, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Kinetics of Antiviral Activity by Human Immunodeficiency
Virus Type 1-Specific Cytotoxic T Lymphocytes (CTL) and Rapid
Selection of CTL Escape Virus In Vitro
C. A.
Van
Baalen,1
M.
Schutten,1
R. C.
Huisman,1
P. H. M.
Boers,1
R. A.
Gruters,1,2 and
A. D. M. E.
Osterhaus1,*
Institute of Virology, Erasmus University,
Rotterdam, The Netherlands,1 and
UMR103, CNRS/Biomerieux, ENS de Lyon, Lyon,
France2
Received 9 February 1998/Accepted 28 April 1998
The antiviral activity of a CD8+ cytotoxic T-lymphocyte
(CTL) clone (TCC108) directed against a newly identified
HLA-B14-restricted epitope, human immunodeficiency virus type 1 (HIV-1)
Rev(67-75) SAEPVPLQL, was analyzed with respect to its kinetics of
target cell lysis and inhibition of HIV-1 production. Addition of
TCC108 cells or CD8+ reverse transcriptase-specific CTLs to
HLA-matched CD4+ T cells at different times after infection
with HIV-1 IIIB showed that infected cells became susceptible to
CTL-mediated lysis before peak virus production but after the onset of
progeny virus release. When either of these CTLs were added to part of
the infected cells immediately after infection, p55 expression and
virus production were significantly suppressed. These data
support a model in which CTLs, apart from exerting cytolytic activity
which may prevent continued virus release, can interfere with viral
protein expression during the eclipse phase via noncytolytic
mechanisms. TCC108-mediated inhibition of virus replication in
peripheral blood mononuclear cells caused rapid selection of a virus
with a mutation (69E
K) in the Rev(67-75) CTL epitope which abolished
recognition by TCC108 cells. Taken together, these data suggest that
both cytolytic and noncytolytic antiviral mechanisms of CTLs can be
specifically targeted to HIV-1-infected cells.
*
Corresponding author. Mailing address: Erasmus
University Rotterdam, Institute of Virology, Room EE17-26, P.O. Box
1738, 3000 DR Rotterdam, The Netherlands. Phone: 31 10 4088066. Fax: 31 10 4365145. E-mail: Osterhaus{at}viro.fgg.eur.nl.
J Virol, August 1998, p. 6851-6857, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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