Expanded tropism of primary human immunodeficiency virus type 1 R5 strains to CD4(+) T-cell lines determined by the capacity to exploit low concentrations of CCR5.
Human immunodeficiency virus type 1 (HIV-1) non-syncytium-inducing (NSI) strains predominantly use the chemokine receptor CCR5, while syncytium-inducing (SI) strains use CXCR4. In vitro, SI isolates infect and replicate in a range of CD4(+) CXCR4(+) T-cell lines, whereas NSI isolates usually do not. Here we describe three NSI strains that are able to infect two CD4(+) T-cell lines, Molt4 and SupT1. For one strain, a variant of JRCSF selected in vitro, replication on Molt4 was previously shown to be conferred by a single amino-acid change in the V1 loop (M.T. Boyd et al., J. Virol. 67:3649-3652, 1993). On CD4(+) cell lines expressing different coreceptors, these strains use CCR5 predominantly and do not replicate in CCR5-negative peripheral blood mononuclear cells derived from individuals homozygous for Delta32 CCR5. Furthermore, infection of Molt4 and SupT1 by each of these three strains is potently inhibited by ligands for CCR5, including 2D7, a monoclonal antibody specific for CCR5. CCR5 mRNA was present in both Molt4 and SupT1 by reverse transcription-PCR, although CCR5 protein could not be detected either on the cell surface or in intracellular vesicles. The expanded tropism of the three strains shown here is therefore not due to adaptation to a new coreceptor but due to the capacity to exploit extremely low levels of CCR5 on Molt4 and SupT1 cells. This novel tropism observed for a subset of primary HIV-1 isolates may represent an extended tropism to new CD4(+) cell types in vivo.
Dejucq
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Section of Virology, Chester Beatty Laboratories, Institute of Cancer Research, London SW3 6JB, United Kingdom.
Simmons
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G
Clapham
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PR
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008024:Ligands; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D008024:Ligands; D019713:Receptors, CCR5; D019718:Receptors, CXCR4