A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction

Willett, B. J. , McMonagle, E. L., Logan, N., Samman, A. and Hosie, M. J. (2008) A single site for N-linked glycosylation in the envelope glycoprotein of feline immunodeficiency virus modulates the virus-receptor interaction. Retrovirology, 5(77), (doi:10.1186/1742-4690-5-77)

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Publisher's URL: http://dx.doi.org/10.1186/1742-4690-5-77

Abstract

Feline immunodeficiency virus (FIV) targets helper T cells by attachment of the envelope glycoprotein (Env) to CD134, a subsequent interaction with CXCR4 then facilitating the process of viral entry. As the CXCR4 binding site is not exposed until CD134-binding has occurred then the virus is protected from neutralising antibodies targeting the CXCR4-binding site on Env. Prototypic FIV vaccines based on the FL4 strain of FIV contain a cell culture-adapted strain of FIV Petaluma, a CD134-independent strain of FIV that interacts directly with CXCR4. In addition to a characteristic increase in charge in the V3 loop homologue of FIV<sub>FL4</sub>, we identified two mutations in potential sites for N-linked glycosylation in the region of FIV Env analogous to the V1-V2 region of HIV and SIV Env, T271I and N342Y. When these mutations were introduced into the primary GL8 and CPG41 strains of FIV, the T271I mutation was found to alter the nature of the virus-CD134 interaction; primary viruses carrying the T271I mutation no longer required determinants in cysteine-rich domain (CRD) 2 of CD134 for viral entry. The T271I mutation did not confer CD134-independent infection upon GL8 or CPG41, nor did it increase the affinity of the CXCR4 interaction, suggesting that the principal effect was targeted at reducing the complexity of the Env-CD134 interaction.

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 Logan, Miss Nicola
Authors: Willett, B. J., McMonagle, E. L., Logan, N., 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
Copyright Holders:Copyright © 2008 Willett et al.
First Published:First published in Retrovirology 5(77)
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