CD8(-LYMPHOCYTE-MEDIATED INHIBITION OF HIV-1 LONG TERMINAL REPEAT TRANSCRIPTION - A NOVEL ANTIVIRAL MECHANISM() T)

HIV-1 infection evokes a vigorous antiviral response that may particip ate in resolving the initial peak of plasma viremia and maintenance of the asymptomatic state. CD8(+) T lymphocytes of HIV-1-infected indivi duals play a critical role in the cellular anti-HIV response. In agree ment with previous reports, we observed a potent suppressive effect on HIV-1 production from autologous CD4(+) T lymphocytes by CD8(+) T lym phocytes from asymptomatic HIV-1-infected individuals. To elucidate th e mechanism(s) of the nonlytic suppressive antiviral activity, we exam ined the effect of CD8(+) T Iymphocytes on the transcriptional activit y of the HIV-1 promoter (HIV-LTR). CD8(+) lymphocytes from HIV-1-infec ted asymptomatic individuals suppressed fat-mediated HIV-LTR transcrip tion in CD4(+) lymphocytes. HIV-LTR transcriptional activity was suppr essed by CD8 lymphocytes to an extent similar to tat-mediated transcri ption whereas CMV immediate early gene promoter activity was not affec ted. In contrast to the suppressive effect seen with CD8(+) lymphocyte s from HIV-1-infected individuals, CD8+ lymphocytes from uninfected in dividuals did not significantly inhibit tat-mediated or HIV-LTR transc ription. The transcriptional inhibitory activity was not MHC class I r estricted and could be mediated by a soluble factor(s). Supernatants f rom some CD8(+) T lymphocyte cultures from HIV-1(+) individuals exerte d an inhibitory effect on tat-mediated HIV-LTR transcription comparabl e to that seen with CD8(+) cells. In conclusion, CD8(+) lymphocytes fr om asymptomatic HIV-1(+) individuals could suppress virus production b y inhibiting HIV-1 gene expression. This suppressive effect of CD8(+) T lymphocytes on HIV-1 promoter activity could play a role in the regu lation of HIV-1 replication during the asymptomatic period of HIV-1 in fection.