Co-receptor use by HIV and inhibition of HIV infection by chemokine receptor ligands.

Abstract

Human and simian immunodeficiency viruses (HIV and SIV) require a seven transmembrane chemokine (7TM) receptor in addition to CD4 for efficient entry into cells. CCR5 and CXCR4 act as major co-receptors for non-syncytium-inducing and syncytium-inducing strains respectively. We have examined the co-receptor requirement for HIV-1 infection of cells of macrophage lineage. Both CCR5 and CXCR4 can operate as functional co-receptors for infection in these cell types. Other co-receptors utilised by multi-co-receptor-using strains of HIV-1, including CCR3 and STRL33, were not used for macrophage infection. HIV-2 and SIV strains, however, can replicate in both peripheral blood mononuclear cells (PBMCs) and other primary cell types such as fibroblasts independently of CCR5 or CXCR4. HIV co-receptors, particularly CCR5, will be major targets for new therapeutics in this decade. We have therefore investigated different chemokines and derivatives that bind co-receptors for their capacity to inhibit HIV infection. These included derivatives of a CCR5 ligand, RANTES, with modified N-termini as well as Kaposi's sarcoma-associated herpesvirus-encoded chemokines that bind a wide range of co-receptors, including CCR5, CXCR4, CCR3 and CCR8, as well as the orphan 7TM receptors GPR1 and STRL33. One compound, aminooxypentane or AOP-RANTES, was a particularly potent inhibitor of HIV infection on PBMCs, macrophages and CCR5+ cell lines and demonstrated the great promise of therapeutic strategies aimed at CCR5.

• Authors: G Simmons, J D Reeves, S Hibbitts, J T Stine, P W Gray, A E Proudfoot, P R Clapham
• Journal: Immunological reviews (Immunol Rev) Vol. 177 Pg. 112-26 (Oct 2000) ISSN: 0105-2896 [Print] England
• PMID: 11138769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Chemokines
• Ligands
• Receptors, Chemokine
• Receptors, HIV

Topics

• Chemokines (immunology)
• HIV Infections (immunology)
• HIV-1 (immunology)
• HIV-2 (immunology)
• Humans
• Ligands
• Receptors, Chemokine (immunology)
• Receptors, HIV (immunology)