Yi Y, Rana S, Collman RG; Keystone Symposia on Molecular and Cellular Biology: 1998 HIV Pathogenesis and Treatment.
Keyst Symp Mol Cell Biol Keyst Symp Mol Cell Biol. 1998 Mar 13-19; 80 (abstract no. 3085).
University of Pennsylvania, Philadelphia, PA.
M-tropic HIV-1 strains infect macrophages and lymphocytes but not CD4+ cell lines, while T-tropic isolates infect CD4+ cell lines and lymphocytes but not macrophages. Dual-tropic isolates infect all 3 cell types. The cellular basis for tropism is determined at least in part by the selective use of chemokine receptors as entry cofactors since T-tropic strains generally use CXCR-4, M-tropic strains generally use CCR5, and some dual-tropic isolates may use both CCR5 and CXCR-4. We used macrophages from CCR5delta32 homozygous donors to address the cellular basis for tropism. CCR5-deficient macrophages were resistant to CCR5-dependent M-tropic strains but permissive for a dual-tropic isolate (89.6) that uses CCR5, CXCR-4, CCR2b, CCR3 and CCR8. Entry by 89.6 into CCR5-deficient macrophages was mediated by CXCR-4, since it was blocked by an anti-CXCR-4 mAb and the CXCR-4 ligand SDF but not by CCR2b or CCR3 ligands. RT-PCR and FACS confirmed macrophage CXCR-4 expression, whereas CCR3 and CCR8 were not detected and CCR2 was variable. We identified several other dual-tropic isolates that also entered CCR5-deficient macrophages via CXCR-4, including some competent to use both CCR5 and CXCR-4 and some restricted to CXCR-4 only. Since prototype T-tropic strains cannot utilize macrophage CXCR-4, this shows that HIV-1 strains differ in how they utilize chemokine receptors for entry, and that the ability of a chemokine receptor to mediate entry differs depending on the cell in which it is expressed. Thus, macrophage resistance to T-tropic HIV-1 results not from lack of CXCR-4 but from the inability of those strains to utilize it as expressed on macrophages. In addition, dual-tropism can result either from use of both CCR5 and CXCR-4, or from a CXCR-4-restricted virus that is able to use macrophage CXCR-4.
Publication Types:
Keywords:
- Antigens, CD4
- CCR8 protein, human
- Cell Line
- HIV-1
- Macrophages
- Receptors, CCR5
- Receptors, Chemokine
- immunology
Other ID:
UI: 102236848
From Meeting Abstracts