CD8(+) T-CELLS SUPPRESS HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION BY INHIBITING VIRAL TRANSCRIPTION

CD8(+) cells from human immunodeficiency virus (HIV)-infected individuals suppress HIV replication in cultured CD4(+) cells from a noncytolytic mechanism that involves a secreted CD8(+)-cell antiviral factor (CAF). The results of this study suggest that CD8(+) cells, as well as CAF, arrest HIV replication at the level of viral transcription. Culturing naturally infected CD4(+) cells actively producing HIV with autologous CD8(+) cells or a 50% dilution of culture fluids from these cells results in a >80% reduction in the number of cells expressing HIV antigens and RNA. This effect was observed within 2 days after exposure to CD8(+) cells but required 6 days in the presence of CAF-containing culture fluids to reach the same extent of HIV suppression. Northern blot analysis of CD4(+) cell extracts revealed that all viral RNA species (unspliced and single and doubles spliced) were reduced in quantity to a similar extent. CAF-containing culture fluids also had a direct inhibitory effect on HIV long terminal repeat (LTR)-driven transcription in HIV-infected 1G5 cells carrying an LTR-luciferase construct. Suppression of basal levels of LTR-driven transcription was not detected. Thus, the results suggest that the noncytolytic CD8(+) cell antiviral activity observed in HIV infection exerts its effects, at least in part, by specifically interrupting HIV transcription. These findings could help in developing therapies for HIV infection.