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. 2008 Nov;82(21):10953-8.
doi: 10.1128/JVI.01312-08. Epub 2008 Aug 20.

Genetically Divergent Strains of Feline Immunodeficiency Virus From the Domestic Cat (Felis Catus) and the African Lion (Panthera Leo) Share Usage of CD134 and CXCR4 as Entry Receptors

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Genetically Divergent Strains of Feline Immunodeficiency Virus From the Domestic Cat (Felis Catus) and the African Lion (Panthera Leo) Share Usage of CD134 and CXCR4 as Entry Receptors

William A McEwan et al. J Virol. .
Free PMC article

Abstract

The env open reading frames of African lion (Panthera leo) lentivirus (feline immunodeficiency virus [FIV(Ple)]) subtypes B and E from geographically distinct regions of Africa suggest two distinct ancestries, with FIV(Ple)-E sharing a common ancestor with the domestic cat (Felis catus) lentivirus (FIV(Fca)). Here we demonstrate that FIV(Ple)-E and FIV(Fca) share the use of CD134 (OX40) and CXCR4 as a primary receptor and coreceptor, respectively, and that both lion CD134 and CXCR4 are functional receptors for FIV(Ple)-E. The shared usage of CD134 and CXCR4 by FIV(Fca) and FIV(Ple)-E may have implications for in vivo cell tropism and the pathogenicity of the E subtype among free-ranging lion populations.

Figures

FIG. 1.
FIG. 1.
Receptor utilization by FIVFca and FIVPle-E. HIV-luciferase pseudotypes were prepared bearing the Envs of either FIVFca or FIVPle-E and used to infect MCC cells stably transduced with retroviral vectors bearing feline (domestic cat) CD134 (fCD134), feline CD134 CRD1/human CD134 chimera (fCRD1/hCD134), human CD134 (hCD134), or vector only (control) (A); NP2 cells transduced with retroviral vectors bearing lion CD134, lion CXCR4, feline CD134, or feline CXCR4 in combination (B); or lion CD134, lion CXCR4, feline CD134, or feline CXCR4 alone or lion CXCR4 in combination with lion or feline CD134 (C). Cells were infected with pseudotypes bearing FIVPle-E or FIVFca-GL8 (A); FIVFca-PPR, GL8, 1419, TM2, or CPG41 (50) (B); or FIVPle-E or FIVFca-GL8 (C). Histograms are representative of the results of at least two independent experiments and display means ± standard errors (n = 3).
FIG. 2.
FIG. 2.
Syncytium formation in FIVPle-E env-transfected cells. AH927 cells expressing feline CXCR4 (A, C) or feline CXCR4 plus feline CD134 (B, D) were transfected with eukaryotic expression vectors bearing FIVPle-E (A, B) or FIVFca-GL8 (C, D) env. Monolayers were fixed and stained at 48 h posttransfection, and photographed representative images are shown.
FIG. 3.
FIG. 3.
Sensitivity of FIVPle-E to AMD3100 and soluble CD134L. MYA-1 T cells were infected with HIV(FIV)-luciferase pseudotypes bearing Envs from FIVPle-E or FIVFca-GL8 and B2542 in the presence of increasing concentrations of CXCR4 antagonist AMD3100 (A, C) or soluble Fc-TNC-CD134L (sFc-TNC-CD134L) (B, D). (A, B) Luciferase activity at 72 h postinfection. Each point represents the mean (n = 3) ± standard error. CPM, counts per minute. (C, D) Percent infection relative to mean infectivity of control with no antagonist. TNC, tenascin.
FIG. 4.
FIG. 4.
Productive infection with FIVPle-E is CD134 dependent. Canine CLL cells (CLL) or CLL cells stably transduced with retroviral vectors bearing feline (domestic cat) CD134 or vector only (CLL+CD134) were infected with MYA-1 T-cell-grown FIVFca-GL8, FIVPle-E, or FIVPle-B, and viral replication was quantified by nonisotopic reverse transcriptase (RT) assay (colorimetric assay; absorbance at 405 nm).

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