14th International AIDS Conference Barcelona, Spain - July 7-12, 2002

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10049)

Grivel JC, Ito Y, Biancotto A, Margolis L
National Institutes of Health, Bethesda, United States

BACKGROUND: Critical events in HIV disease occur in lymphoid tissue, where HIV-1 infection leads to a massive depletion of CD4+ T cells. While it is firmly established that HIV-1 kills the majority of infected cells, it remains controversial, whether and to what extent uninfected ("bystander") cells are also killed. We address this question using a system of human lymphoid tissue ex vivo.

METHODS: Blocks of human lymphoid tissue were infected with the HIV-1 isolate LAV.04. After estalishing the productive infection of a fraction of tissue target cells, we added Nevirapine, a non-nucleoside reverse transcriptase inhibitor, to prevent de novo infection. CD4 T cells were enumerated using flow cytometry.

RESULTS: Viral replication, as evaluated from p24 concentration in culture medium, was detectable typically at day 6 post-infection and continued to increase until day 9 post-infection, reflecting the increased number of productively infected CD4+ T cells. De novo viral infection was completely inhibited by Nevirapine at 5 é M. We added Nevirapine to HIV-1 infected tissues at different time points after HIV-1 infection was established . Thus, in these tissues, one pool of CD4+ T cells was infected prior to Nevirapine application and continued to produce virus, the other pool of CD4+ T cells resided in the same tissue and remained uninfected. A decrease in CD4+ T cell number in infected tissue became apparent on day 5 post-infection and on day 13 post-infection, CD4 T cells reached 3±+0.5% of uninfected control. After Nevirapine was added, the depletion of CD4+ T cells stopped and their number remained stable. Also, in contrast to infected cells, the bystander T cells do not downregulate CD4.

CONCLUSIONS: In the context of ex vivo HIV-infected human lymphoid tissue productive HIV infection kills infected cells but is not sufficient to cause the death of uninfected CD4+ T cells

020707
A10049

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