AEGiS-14IAC: Interleukin 2 is a poor inducer of HIV reactivation, but enhances viral persistence in lymphocytes.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Interleukin 2 is a poor inducer of HIV reactivation, but enhances viral persistence in lymphocytes.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. WeOrA1347)

Rullas J, Pedraza MA, Martin-Serrano J, Beltran M, Alcami J
Aids Immunopathogenesis Unit. Centro Nacional de Microbiologia. Instituto de Salud Carlos III, Majadahonda, Spain

BACKGROUND: The study of the mechanisms leading to HIV persistence and reactivation represent a major issue in understanding HIV pathogenesis. We have developed an efficient system that allow transfection of a full length HIV provirus in resting peripheral blood lymphocytes. In this model we have addressed the role of IL2 and other cytokines in HIV reactivation from latency and the molecular mechanisms involved.

METHODS: Lymphocytes from seronegative donors [transfected by electroporation with an infectious provirus (NL4.3)] or from HIV-infected patients were activated with IL2, antiCD3, PMA or TNF-a+IL6. In some experiments resting PBMC were transfected and stimulated with IL2 or left untreated for 7 days before activation. HIV replication was assessed by quantifying p24 antigen in supernatants. Cell proliferation was measured by thymidine incorporation and cell cycle progression by propidium iodide staining. Induction of Rel/NF-kB family of transcription factors was analyzed by gel-shift assay.

RESULTS: In contrast with high viral replication induced by CD3, IL2 stimulation resulted in bare replication levels in culture in both HIV-transfected cells and lymphocytes from infected patients. Lack of HIV replication was not due to weak proliferation of IL2 activated lymphocytes. In agreement with these results NF-kB was not induced by IL2 treatment. When transfected PBMC were cultured in the presence of IL2 for 7 days, treatment with PMA, TNF-a or TNFa+IL-6 were able to induce a strong HIV reactivaton. In contrast, no viral replication was detected by such stimuli when PBMC were not previously treated with IL2.

CONCLUSION: IL2 was a poor inducer of HIV reactivation from the state of proviral latency despite the induction of robust lymphocyte proliferation in culture. IL2 treatment for seven days increased HIV persistence in resting lymphocytes, suggesting that this cytokine could enhance the stability and/or integration of proviral DNA.

Keywords: AEGIS, Interleukin-2, HIV Infections, Lymphocytes, HIV Seropositivity, Virus Replication, Tumor Necrosis Factor, Interleukin-6, CD4-Positive T-Lymphocytes, Cytokines, Transfection, T-Lymphocytes, Helper-Inducer, Human, virology, genetics

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