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. 1998 May;72(5):4065-71.
doi: 10.1128/JVI.72.5.4065-4071.1998.

A broad range of chemokine receptors are used by primary isolates of human immunodeficiency virus type 2 as coreceptors with CD4

A McKnight  1 , M T Dittmar, J Moniz-Periera, K Ariyoshi, J D Reeves, S Hibbitts, D Whitby, E Aarons, A E Proudfoot, H Whittle, P R Clapham
Affiliations

A broad range of chemokine receptors are used by primary isolates of human immunodeficiency virus type 2 as coreceptors with CD4

A McKnight et al. J Virol. 1998 May.

Abstract

Like human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), HIV-2 requires a coreceptor in addition to CD4 for entry into cells. HIV and SIV coreceptor molecules belong to a family of seven-transmembrane-domain G-protein-coupled receptors. Here we show that primary HIV-2 isolates can use a broad range of coreceptor molecules, including CCR1, CCR2b, CCR3, CCR4, CCR5, and CXCR4. Despite broad coreceptor use, the chemokine ligand SDF-1 substantially blocked HIV-2 infectivity of peripheral blood mononuclear cells, indicating that its receptor, CXCR4, was the predominant coreceptor for infection of these cells. However, expression of CXCR4 together with CD4 on some cell types did not confer susceptibility to infection by all CXCR4-using virus isolates. These data therefore indicate that another factor(s) influences the ability of HIV-2 to replicate in human cell types that express the appropriate receptors for virus entry.

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Figures

FIG. 1
FIG. 1
Titration of primary HIV-2 isolates on chemokine receptor-expressing U87/CD4 cells. After incubation for 3 to 5 days, cells were fixed and immunostained and infection (FFU per milliliter) was estimated. Error bars indicate standard deviations.
FIG. 2
FIG. 2
Selection of a primary isolate to grow in T-cell lines restricts coreceptor use. prCBL-20 was selected to grow in C8166 cells, and stocks were made in H9 cells (52). The resulting virus was titrated on either the parental U87/CD4 cells or those stably expressing the chemokine receptor CCR1, CCR2b, CCR3, CCR5, or CXCR4. Infection (FFU per milliliter) was calculated after immunostaining of 5-day-old infected cultures. Error bars indicate standard deviations.
FIG. 3
FIG. 3
Detection of homozygous deleted CCR5. CCR5 DNA was amplified from genomic DNA derived from the PBMCs of an individual homozygous for the CCR5 deletion and an individual homozygous for the wild-type CCR5 gene. PCR products were visualized by electrophoresis on a 3% agarose gel. Lanes: M, 1-kb marker; 1, negative control; 2 and 3, 200 and 400 ng of homozygous Δ32 CCR5 PBMC DNA, respectively; 4, negative control; 5 and 6, 200 and 400 ng of wild-type CCR5 PBMC DNA, respectively.
FIG. 4
FIG. 4
Inhibition of infection by prCBL-20, CBL-20, and A-ND with chemokines on wild-type CCR5 and Δ32 CCR5 PBMCs. Infectivity assays with prCBL-20 and A-ND were performed in the absence and presence of the chemokines SDF-1, AOP-RANTES, and MCP-1 either alone or together at the concentrations indicated. Cell targets were either homozygous wild-type or Δ32 CCR5 PBMCs. RT activity in the supernatant on day 5 was determined, and the results are shown as percent inhibition with respect to the control (con.) value. Error bars indicate standard deviations.
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