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Journal of Virology, September 2007, p. 9665-9679, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.01020-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Probing the Interaction between Feline Immunodeficiency Virus and CD134 by Using the Novel Monoclonal Antibody 7D6 and the CD134 (Ox40) Ligand{triangledown}

Brian J. Willett,1* Elizabeth L. McMonagle,1 Nicola Logan,1 O. Brad Spiller,2 Pascal Schneider,3 and Margaret J. Hosie1

Retrovirus Research Laboratory, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, United Kingdom,1 Virus Receptor & Immune Evasion Group, Cardiff University School of Medicine, Henry Wellcome Research Institute, Heath Park, Cardiff CF14 4XN, United Kingdom,2 Department of Biochemistry, University of Lausanne, Ch. des Boveresses 155, CH-1066 Epalinges, Switzerland3

Received 10 May 2007/ Accepted 13 June 2007

The feline immunodeficiency virus (FIV) targets activated CD4-positive helper T cells preferentially, inducing an AIDS-like immunodeficiency in its natural host species, the domestic cat. The primary receptor for FIV is CD134, a member of the tumor necrosis factor receptor superfamily, and all primary viral strains tested to date use CD134 for infection. We examined the expression of CD134 in the cat using a novel anti-feline CD134 monoclonal antibody (MAb), 7D6, and showed that as in rats and humans, CD134 expression is restricted tightly to CD4+, and not CD8+, T cells, consistent with the selective targeting of these cells by FIV. However, FIV is also macrophage tropic, and in chronic infection the viral tropism broadens to include B cells and CD8+ T cells. Using 7D6, we revealed CD134 expression on a B220-positive (B-cell) population and on cultured macrophages but not peripheral blood monocytes. Moreover, macrophage CD134 expression and FIV infection were enhanced by activation in response to bacterial lipopolysaccharide. Consistent with CD134 expression on human and murine T cells, feline CD134 was abundant on mitogen-stimulated CD4+ T cells, with weaker expression on CD8+ T cells, concordant with the expansion of FIV into CD8+ T cells with progression of the infection. The interaction between FIV and CD134 was probed using MAb 7D6 and soluble CD134 ligand (CD134L), revealing strain-specific differences in sensitivity to both 7D6 and CD134L. Infection with isolates such as PPR and B2542 was inhibited well by both 7D6 and CD134L, suggesting a lower affinity of interaction. In contrast, GL8, CPG, and NCSU were relatively refractory to inhibition by both 7D6 and CD134L and, accordingly, may have a higher-affinity interaction with CD134, permitting infection of cells where CD134 levels are limiting.

* Corresponding author. Mailing address: Retrovirus Research Laboratory, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, United Kingdom. Phone: 44 141 330 3274. Fax: 44 141 330 2271. E-mail: b.willett{at}vet.gla.ac.uk

{triangledown} Published ahead of print on 3 July 2007.

Journal of Virology, September 2007, p. 9665-9679, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.01020-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • McEwan, W. A., McMonagle, E. L., Logan, N., Serra, R. C., Kat, P., VandeWoude, S., Hosie, M. J., Willett, B. J. (2008). 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. J. Virol. 82: 10953-10958 [Abstract] [Full Text]  


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