Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

Willett, B. J. , Kraase, M., Logan, N., McMonagle, E. L., Samman, A. and Hosie, M. J. (2010) Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody. Retrovirology, 7(1), p. 38. (doi:10.1186/1742-4690-7-38)

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Publisher's URL: http://dx.doi.org/10.1186/1742-4690-7-38

Abstract

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hosie, Professor Margaret and Willett, Professor Brian and Samman, Mr Ayman and McMonagle, Mrs Elizabeth and Kraase, Mr Martin and Logan, Miss Nicola
Authors: Willett, B. J., Kraase, M., Logan, N., McMonagle, E. L., Samman, A., and Hosie, M. J.
Subjects:Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Retrovirology
Publisher:BioMed Central
ISSN:1742-4690
First Published:First published in Retrovirology 7:38
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.
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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
392061Control of Feline Immunodeficiency Virus InfectionMargaret HosieBiotechnology and Biological Sciences Research Council (BBSRC)BB/D008425/1Centre for Virus Research