AEGiS-12IAC: Simian immunodeficiency virus acute infection and CCR5, CCR1, IFN gamma, RANTES expression in lymphoid tissues.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

Simian immunodeficiency virus acute infection and CCR5, CCR1, IFN gamma, RANTES expression in lymphoid tissues.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:26 (abstract no. 11222)

Cheret A, Le Grand B, Caufour P, Neildez O, Matheux F, Vaslin B, Dormont D
CEA Service De Neurovirologie DSV/DRM, Fontenay AUX Roses, France.

OBJECTIVES: Our aim was to determine whether there is a temporal sequence linking SIV replication and dissemination, the chemokine RANTES and chemokine receptor CCR5 expressions in different tissues during acute infection of macaques inoculated intravenously with a pathogenic primary isolate of SIVmac251. These expressions were compared to those of IFN gamma as an indicator of the development of the immune response and another receptor for RANTES, CCR1, which is not described as a coreceptor for SIV/HIV entry.

METHODS: Four cynomolgus macaques were inoculated intravenously with a pathogenic primary isolate of SIVmac251. We used quantitative RT-PCR to monitor the expression of RANTES, IFN gamma, CCR1 and CCR5 mRNA. This quantification was done concomitantly with fresh isolated peripheral blood mononuclear cells (PBMC), lymph node mononuclear cells (LNMC) and mononuclear cells obtained from bronchoalveolar lavages (BALMC). The kinetics of hematological, virological and immunological changes were investigated simultaneously.

RESULTS: The four animals became infected. Our results suggest an early leukocyte recruitment and viral dissemination to tissues. We demonstrated that active viral replication is concomitant with enhancement of CCR1/CCR5 mRNA expression in PBMC, LNMC and BALMC. Containment of virus replication was associated with enhancement of IFN gamma and RANTES mRNA expression in the different tissues investigated. In BALMC, IFN gamma and RANTES expression closely paralleled a marked increased percentages in CD8+ T lymphocytes.

CONCLUSION: RANTES and CCR mRNA overexpressions highlight the plurality of chemokine and chemokine receptor biological effects with regard to their implication in viral dissemination and the development of an efficient antiviral immune response. New therapeutic strategies interfering with their functions need further investigations.

Keywords: AEGIS, SIV, RANTES, Lymphoid Tissue, Lymph Nodes, Chemokines, Receptors, Chemokine, CD8-Positive T-Lymphocytes, RNA, Messenger, Virus Replication, Gene Expression, virology, genetics, ICA12
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