Chemokine receptors and co-stimulatory molecules: unravelling feline immunodeficiency virus infection.
Feline immunodeficiency virus (FIV) infection of the domestic cat induces an immunodeficiency characterised by a gradual depletion of CD4+ T-helper lymphocytes. The virus targets T-helper cells by way of an interaction between its envelope glycoprotein (Env) and the cell surface molecule CD134 (OX40), a member of the nerve growth factor receptor/tumour necrosis factor receptor superfamily. The Env-CD134 interaction is a necessary prerequisite for the subsequent interaction with CXCR4, the only chemokine receptor identified to date to act as a co-receptor for FIV. As T-helper cell expression of CD134 and CXCR4 is restricted to activated cells, FIV targets selectively antigen-specific T-helper cells. With disease progression the cell tropism of the virus expands; this may be the result of changes in the way in which Env interacts with CD134, a less stringent Env-CD134 interaction enabling the Env to interact more readily with CXCR4 and thus broadening the cell tropism of virus. In contrast, viruses that are present in early infection may have a narrower cell tropism, reflecting a more stringent interaction with CD134. Accordingly, "early" viruses may target CD134-expressing cells more efficiently and be more resistant to neutralising antibody. It is these early viruses that may be transmitted and should be considered as candidates for the development of vaccine regimes and novel therapeutic agents.
Willett
Brian J
BJ
Retrovirus Research Laboratory, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsen Road, Glasgow G61 1QH, United Kingdom. b.willett@vet.gla.ac.uk
Hosie
Margaret J
MJ
D000818:Animals; D002415:Cats; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015686:Gene Products, env / Q000276:immunology*; D016089:Immunodeficiency Virus, Feline / Q000276:immunology*; D008958:Models, Molecular; D053278:OX40 Ligand / Q000276:immunology; D019718:Receptors, CXCR4 / Q000276:immunology*; D053262:Receptors, OX40 / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000821:virology
D015686:Gene Products, env; D053278:OX40 Ligand; D019718:Receptors, CXCR4; D053262:Receptors, OX40