KINETICS OF ANTIVIRAL ACTIVITY BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-SPECIFIC CYTOTOXIC T-LYMPHOCYTES (CTL) AND RAPID SELECTION OF CTL ESCAPE VIRUS IN-VITRO

The antiviral activity of a CD8(+) cytotoxic T-lymphocyte (CTL) clone (TCC108) directed against a newly identified HLA-B14-restricted epitop e, human immunodeficiency virus type 1 (HIV-1) Rev(67-75) SAEPVP LQL, was analyzed with respect to its kinetics of target cell lysis and inh ibition of HIV-1 production. Addition of TCC108 cells or CD8(+) revers e transcriptase-specific CTLs to HLA-matched CD4(+) T cells at differe nt times after infection with HIV-1 IIIB showed that infected cells be came susceptible to CTL-mediated lysis before peak virus production bu t 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. The se data support a model in which CTLs, apart from exerting cytolytic a ctivity which may prevent continued virus release, can interfere with viral protein expression during the eclipse phase via noncytolytic mec hanisms. TCC108-mediated inhibition of virus replication in peripheral blood mononuclear cells caused rapid selection of a virus with a muta tion (69E-->K) in the Rev(67-75) CTL epitope which abolished recogniti on by TCC108 cells. Taken together, these data suggest that both cytol ytic and noncytolytic antiviral mechanisms of CTLs can be specifically targeted to HIV-1-infected cells.