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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 (69Eright-arrowK) 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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