Enlighten
Research publications by members of the University of Glasgow
home > services > Enlighten

Shared usage of the chemokine receptor CXCR4 by the feline and human immunodeficiency viruses

Willett, B.J., Picard, L., Hosie, M.J., Turner, J.D., Adema, K., and Clapham, P.R. (1997) Shared usage of the chemokine receptor CXCR4 by the feline and human immunodeficiency viruses. Journal of Virology, 71 (9). pp. 6407-6415. ISSN 0022-538X

[img] Text
pubmed_redirect.htm

4Kb

Publisher's URL: http://jvi.asm.org/cgi/content/abstract/71/9/6407

Abstract

Feline immunodeficiency virus (FIV) induces a disease state in the domestic cat that is similar to AIDS in human immunodeficiency virus (HIV)-infected individuals. As with HIV, FIV can be divided into primary and cell culture-adapted isolates. Adaptation of FIV to replicate and form syncytia in the Crandell feline kidney (CrFK) cell line is accompanied by an increase in the net charge of the V3 loop of the envelope glycoprotein, mirroring the changes observed in the V3 loop of HIV gp120 with the switch from a non-syncytium-inducing phenotype to a syncytium-inducing phenotype. These data suggest a common mechanism of infection with FIV and HIV. In this study, we demonstrate that cell culture-adapted strains of FIV are able to use the alpha-chemokine receptor CXCR4 for cell fusion. Following ectopic expression of human CXCR4 on nonpermissive human cells, the cells are able to fuse with FIV-infected feline cells. Moreover, fusion between FIV-infected feline cells and CXCR4-transfected human cells is inhibited by both anti-CXCR4 and anti-FIV antibodies. cDNAs encoding the feline CXCR4 homolog were cloned from both T-lymphoblastoid and kidney cell lines. Feline CXCR4 displayed 94.9% amino acid sequence identity with human CXCR4 and was found to be expressed widely on cell lines susceptible to infection with cell culture-adapted strains FIV. Ectopic expression of feline CXCR4 on human cells rendered the cells susceptible to FIV-dependent fusion. Moreover, feline CXCR4 was found to be as efficient as human CXCR4 in supporting cell fusion between CD4- expressing murine fibroblast cells and either HIV type 1 (HIV-1) or HIV- 2 Env-expressing human cells. Previous studies have demonstrated that feline cells expressing human CD4 are not susceptible to infection with HIV-1; therefore, further restrictions to HIV-1 Env-dependent fusion may exist in feline cells. As feline and human CXCR4 support both FIV- and HIV-dependent cell fusion, these results suggest a close evolutionary link between FIV and HIV and a common mechanism of infection involving an interaction between the virus and a member of the seven-transmembrane domain chemokine receptor family of molecules.

Item Type:Article
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Willett, Prof Brian
Authors: Willett, B.J., Picard, L., Hosie, M.J., Turner, J.D., Adema, K., and Clapham, P.R.
Subjects:S Agriculture > SF Animal culture > SF600 Veterinary Medicine
Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
Journal Name:Journal of Virology
Journal Abbr.:J. Virol.
ISSN:0022-538X
ISSN (Online):1098-5514

University Staff: Request a correction | Enlighten Editors: Update this record

Downloads per month over past year

View more statistics