AEGiS-12IAC: Study of co-receptors used by NSI HIV-1 strains that infect CD4+ T cell lines, Molt4 and SupT1.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

Study of co-receptors used by NSI HIV-1 strains that infect CD4+ T cell lines, Molt4 and SupT1.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:4 (abstract no. 11111)

Dejucq N, Simmonds G, Hibbitts S, Clapham P
Institute of Cancer Research, London, UK.

BACKGROUND: Non-syncytium-inducing (NSI) CCR5-using strains usually infect macrophages but not T cell lines. A variant of JR-CSF (called C3) selected for replication in the CD4+ T-cell lines Molt4 and SupT1 differed by a single amino-acid change in the V1 loop of gp 120 (Boyd et al., 1993). The aim of this study was therefore to assess the co-receptor use by C3 and other Molt4/SupT1 tropic primary HIV-1 strains.

METHODS: To check co-receptor-use by C3 and other HIV-1 strains, we used the human U87 and the feline CCC cell lines transfected with CD4 and the following chemokine receptors: CCR1, CCR2b, CCR3, CXCR4, CCR5, CCR8, Bob, Bonzo, GPR1 or V28. The expression of known chemokine receptors was assessed on Molt4 and SupT1 using RT-PCR, flow cytometry analysis and confocal microscopy. Inhibition of infection by different chemokines was assessed. Infection of Δ32/Δ32 CCR5 PBMC by C3 and other Molt4/SupT1 NSI strains was studied.

RESULTS: C3 and three other NSI strains that infect Molt4/SupT1 used CCR5 only and did not infect U87 or CCC cells transfected with any other co-receptors. Molt4 and SupT1 were shown to express mRNAs coding for CXCR4, CCR5, CCR3 and Bonzo. CCR5 and CCR3 were however barely undetectable on the cell surface. Inhibition experiments using AOP RANTES, a strong inhibitor of viral entry for strains using either CCR3 or CCR5, blocked infection of both Molt4 and SupT1. Eotaxin, a CCR3 ligand, had no effect on the viral replication, while MIP1 beta, a specific ligand for CCR5, totally inhibited the infection. No infection of Δ32/Δ32 CCR5 PBMC by C3 or other Molt4/SupT1 tropic strains was observed, even after long term culture.

CONCLUSIONS: Our results indicate that some HIV-1 strains with an expanded tropism for Molt4 and SupT1 have no change in co-receptor use and use CCR5 for infection of these cell lines. The implications of these results for HIV-1 co-receptor use and cell tropism in vivo will be discussed.

Keywords: AEGIS, Antigens, CD4, HIV-1, T-Lymphocytes, Virus Replication, Receptors, Chemokine, Chemokines, Chemokines, CC, Macrophages, Giant Cells, Cell Line, Greece, eotaxin, Animal, Cats, Human, immunology, virology, ICA12
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