AEGiS-11IAC: On the mechanism of C-C chemokines (RANTES, MIP-1alpha and MIP-1beta) mediated inhibition of HIV.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

On the mechanism of C-C chemokines (RANTES, MIP-1alpha and MIP-1beta) mediated inhibition of HIV.

Int Conf AIDS 1996 Jul 7-12; 11:227 (abstract no. Tu.A.394)
Garzino-Demo A, Gallo RC, DeVico AL, Cocchi F, Lusso P, Arya SK; Institute of Human Virology, MBC, UMBI, Baltimore, MD, USA. Fax: (410) 706-8184.

OBJECTIVES: The C-C chemokines RANTES, MIP-1alpha and MIP-1beta were identified as the major HIV suppressive factors released by CD8+ T lymphocytes. To understand the mechanism of action and specifically to explore the possibility that such suppressive factors may inhibit HIV RNA transcription, the effect of these chemokines on the basal and Tat-induced HIV-1 LTR-directed gene expression was studied.

METHODS: The effects of recombinant chemokines and/or conditioned medium from CD8+ cells were studied by determining their modulation of HIV-1 LTR directed reporter CAT gene expression in transiently and stably transfected CD4+ T-cell lines, in the presence or absence of Tat. In addition, their effect on virus expression in CD4- T-cells transfected with replication competent proviral clones of HIV-1, HIV-2, and SIV was measured by a core antigen capture assays.

RESULTS: Treatment of CD4+ T-cells infected with HIV-1 with the recombinant chemokines and crude CD8+ T-cell derived conditioned medium lead to a marked suppression of HIV-1 RNA synthesis as analyzed by Northern Blot hybridization. In contrast, virus production in CD4- cells transfected with molecular clones of HIV-1, HIV-2, and SIV was not affected. Further, chemokines and CD8+ T-cell conditioned medium did not down-modulate LTR-directed CAT gene expression in transiently or stably transfected T-cell lines.

CONCLUSIONS: Our results suggest that C-C chemokines and conditioned media from CD8+ cells inhibit HIV replication by affecting a step other than the initiation of transcription. This is in contrast to the previous reports by others of trascriptional down-modulation of HIV-1 expression by factor(s) secreted by CD8+ cells.

Keywords: AEGIS, Macrophage Inflammatory Protein-1, RANTES, Chemokines, CC, HIV Long Terminal Repeat, HIV-1, CD8-Positive T-Lymphocytes, Virus Replication, HIV-2, Chemokines, SIV, Antigens, CD4, Antigens, CD8, Transcription, Genetic, Cats, Animal, genetics, virology, ICA11

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TuA394