AEGiS-11IAC: Chemokines regulate endogenous HIV replication: enhancement by MCP-1 and suppression by RANTES.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Chemokines regulate endogenous HIV replication: enhancement by MCP-1 and suppression by RANTES.

Int Conf AIDS 1996 Jul 7-12; 11:226 (abstract no. Tu.A.392)
Poli G, Biswas P, Delfanti F, Sozzani S, Alfano M, Moretti GL, Lazzarin A, Mantovani A, Vicenzi E; San Raffaele Scientific Institute, Milan, Italy. Fax: 39-2-2643.7989.

OBJECTIVE: To evaluate the role of chemokines on HIV replication in primary cultures of infected individuals.

METHODS: Chemokine concentrations were determined during HIV isolation from either total PBMC or CD8-depleted PBMC of long term non progressors (LTNP). CD8-depleted PBMC cultures from other HIV-infected individuals with CD4 counts between 200 and 500 cells/mm3 were maintained up to 30 days in vitro according to two protocols: 1. Cells were first stimulated by PHA and then maintained in IL-2-enriched medium in the presence or absence of recombinant (r) chemokines (direct culture); 2. cells were co-cultivated with allogeneic PHA blasts from seronegative individuals in the presence or absence of r-chemokines (Coculture). Supernatants were tested for the presence of either RT activity or p24 gag Ag by ELISA (Coulter).

RESULTS: Determination of the chemokine contents of supernatants during isolation either from PBMC or CD8-depleted PBMC of LTNP revealed that several chemokines, including RANTES, MIP-1a, MIP-1b, MCP-1, and IL-8 are released at concentrations of ng/ml. No distinctive patterns of chemokine concentrations were observed in the presence or absence of CD8(+) cells, even when HIV isolation was accomplished exclusively after removal of this fraction of PBMC. Virus production from ex-vivo CD8-depleted PBMC of HIV-infected individuals was demonstrated in a total of 12 cultures or co-cultures. No clear modulatory effects were observed by addition of different chemokines, including MCP-3, IP10, and IL-8 (100 ng/ml) to the cells. In sharp contrast, the same concentrations of MCP-1 and RANTES significantly enhanced in 50% and suppressed in 80%, respectively, HIV replication compared to control cultures. MIP-1a consistently caused a partial (50-90%) inhibition of virus production.

CONCLUSIONS: Chemokines exert important, although opposite effects on HIV replication in primary CD8-depleted PBMC obtained from infected individuals. These results suggest that the extent of latent vs actively replicating infected cells may be under the control of different chemokines exerting divergent effects on virus expression and spreading.

Keywords: AEGIS, RANTES, HIV, Chemokines, Monocyte Chemoattractant Protein-1, Virus Replication, Monocyte Chemoattractant Proteins, HIV Infections, Antigens, CD8, HIV Long Terminal Repeat, Anti-HIV Agents, HIV Core Protein p24, Interleukin-2, monocyte chemoattractant protein-3, In Vitro, virology, genetics, ICA11

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TuA392