Enforced covalent trimerisation of soluble feline CD134 (OX40)-ligand generates a functional antagonist of feline immunodeficiency virus

Willett, B. J. , McMonagle, E. L., Logan, N., Schneider, P. and Hosie, M. J. (2009) Enforced covalent trimerisation of soluble feline CD134 (OX40)-ligand generates a functional antagonist of feline immunodeficiency virus. Molecular Immunology, 46(6), pp. 1020-1030. (doi:10.1016/j.molimm.2008.08.271)

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Publisher's URL: http://dx.doi.org/10.1016/j.molimm.2008.08.271

Abstract

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 tumour necrosis factor receptor superfamily (TNFRSF) and all primary viral strains tested to date use CD134 for infection. To investigate the effect of the natural ligand for CD134 on FIV infection, feline CD134L was cloned and expressed in soluble forms. However, in contrast to murine or human CD134L, soluble feline CD134L (sCD134L) did not bind to CD134. Receptor-binding activity was restored by enforced covalent trimerisation following the introduction of a synthetic trimerisation domain from tenascin (TNC). Feline and human TNC-CD134Ls retained the species-specificity of the membrane-bound forms of the ligand while murine TNC-CD134L displayed promiscuous binding to feline, human or murine CD134. Feline and murine TNC-CD134Ls were antagonists of FIV infection; however, potency was both strain-specific and substrate-dependent, indicating that the modulatory effects of endogenous sCD134L, or exogenous CD134Lbased therapeutics, may vary depending on the viral strain.

Item Type:Articles
Keywords:CD134, CD134L, OX40, OX40L, CD252, FIV, HIV, AIDS
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hosie, Professor Margaret and Willett, Professor Brian and McMonagle, Mrs Elizabeth and Logan, Miss Nicola
Authors: Willett, B. J., McMonagle, E. L., Logan, N., Schneider, P., and Hosie, M. J.
Subjects:S Agriculture > SF Animal culture > SF600 Veterinary Medicine
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Molecular Immunology
Publisher:Elsevier
ISSN:0161-5890
ISSN (Online):1872-9142
Published Online:01 February 2009
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
363381Rational Design of a Lentiviral VaccineMargaret HosieMedical Research Council (MRC)G0300387Centre for Virus Research