AEGiS-12IAC: SIVcpz-ant causes non-escalating immune activation and uses multiple co-receptors in chimpanzees.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

SIVcpz-ant causes non-escalating immune activation and uses multiple co-receptors in chimpanzees.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:24 (abstract no. 11210)

Kestens L, Ondoa P, Vereecken K, McKnight A, Dittmar MT, Davis D, Heeney JL, Van der Groen G
Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium.

OBJECTIVE: To follow-up the systemic immune activation in SIV cpz-ant infected chimpanzees in relation to co-receptor usage.

DESIGN: Prospective controlled study.

METHODS: Systemic immune activation has been studied longitudinally in a naturally infected (Ch-No) and an experimentally infected (Ch-Ni) chimpanzee for 10 and 2 years respectively. Five non-infected chimpanzees served as controls. HLA-DR and CD38 expression were measured on CD8+ T cells in freshly obtained whole blood. Co-receptor use of sequential cell-associated isolates was studied using transfected U87 cell lines expressing human CD4 and the chemokine receptors CCR1, CCR2b, CCR3, CCR5 and CXCR4. Recombinant RANTES, MIP1 alpha and SDF1 alpha were used to assess their blocking capacity on in vitro virus replication.

RESULTS: Both SIVcpz-ant-infected chimpanzees showed no clinical signs of infection and had normal CD4 T cell counts and normal proliferative responses to mitogens and recall antigens. Compared to uninfected controls, Ch-No and Ch-Ni have chronically increased HLA-DR and CD38 expression on CD8+ T cells but markedly less than observed in HIV-infected humans. All sequential Ch-No virus isolates displayed a dominant CCR5 co-receptor usage which was confirmed by in vitro suppression of virus replication by RANTES, MIP1 alpha and MIP1 beta. In Ch-No a progressive decrease of HLA-DR expression on CD8+ T cells over time was inversely correlated with an increased tendency of SIVcpz-ant to broaden its co-receptors usage. All SIVcpz-ant isolates of Ch-Ni displayed a less dominant CCR5 usage than the isolates of Ch-No.

CONCLUSION: SIVcpz infection is associated with a non-escalating systemic immune activation. All SIVcpz isolates use the CCR5 co-receptor. Longitudinally, they cycle between sole use of CCR5 and heterogeneous use of all co-receptors studied.

Keywords: AEGIS, Pan troglodytes, Receptors, CCR5, Receptors, HIV, SIV, HIV Infections, RANTES, Virus Replication, Receptors, Chemokine, Antigens, CD4, T-Lymphocytes, HIV Envelope Protein gp120, HIV, HIV Seropositivity, HIV Core Protein p24, Ants, Antigens, CD8, Prospective Studies, Greece, Animal, Human, In Vitro, virology, immunology, ICA12
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