CD8(+)-cell antiviral factor activity is not restricted to human immunodeficiency virus (HIV)-specific T cells and can block HIV replication after initiation of reverse transcription

CD8(+) lymphocytes from human immunodeficiency virus (HV)-infected patients can suppress in vitro HIV replication in CD4(+) T cells by a noncytolytic mechanism involving secreted CDS'-cell antiviral factor(s) (CAF). Using an HIV Nef-specific cytotoxic-T-lymphocyte (CTL) line and autologous CD4(+) T cells infected with a nef-deleted HIV-1 virus, we demonstrated that, after a priming antigenic stimulation, this suppression does not require the pres ence of the specific antigen during the effector phase. Furthermore, using an Epstein-Barr virus (EBV)-specific CTL line from an HIV-seronegative dono r, we demonstrated that the ability to inhibit HIV replication in a noncyto lytic manner is not restricted to Hn:-specific effector cells; indeed, EBV- specific CTL were as efficient as HN-specific effectors in suppressing R5 o r X4 HIV-1 strain replication in vitro. This HIV-suppressive activity media ted by a soluble factor(s) present in the culture supernatant was detectabl e for up to 14 days following stimulation of EBV-specific CD8(+) cells with the cognate epitope peptide. Following acute infection of CEM cells with a n X4 strain of HIV-1, EBV-specific CTL line supernatant containing AN-suppr essive activity did not block virus entry but was shown to interfere with v irus replication after the first template snitching of reverse transcriptio n. Our results suggest that the noncytolytic control of HIV replication by EBV-specific CD8(+) T lymphocytes corresponded to a CAF-like activity and t hus demonstrate that CAF. production may not be restricted to CTL induced d uring HIV disease. Moreover, CAF acts after reverse transcription at least for X4 isolate replication inhibition.