Kinetics of Antiviral Activity by Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes (CTL) and Rapid Selection of CTL Escape Virus In Vitro

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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-restrictedepitope, human immunodeficiency virus type 1 (HIV-1) Rev(67-75)SAEPVPLQL, was analyzed with respect to its kinetics of targetcell lysis and inhibition of HIV-1 production. Addition of TCC108cells or CD8⁺ reverse transcriptase-specific CTLs to HLA-matched CD4⁺ T cells at different times after infection with HIV-1 IIIB showedthat infected cells became susceptible to CTL-mediated lysis beforepeak virus production but after the onset of progeny virus release.When either of these CTLs were added to part of the infected cellsimmediately after infection, p55 expression and virus productionwere significantly suppressed. These data support a model in whichCTLs, apart from exerting cytolytic activity which may preventcontinued virus release, can interfere with viral protein expressionduring the eclipse phase via noncytolytic mechanisms. TCC108-mediatedinhibition of virus replication in peripheral blood mononuclearcells caused rapid selection of a virus with a mutation (69E $right-arrow$ K)in the Rev(67-75) CTL epitope which abolished recognition by TCC108cells. Taken together, these data suggest that both cytolyticand noncytolytic antiviral mechanisms of CTLs can be specificallytargeted to HIV-1-infected cells.

^* Corresponding author. Mailing address: Erasmus University Rotterdam, Institute of Virology, Room EE17-26, P.O. Box 1738, 3000DR Rotterdam, The Netherlands. Phone: 31 10 4088066. Fax: 31 104365145. 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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