Feline immunodeficiency virus targets activated CD4+ T cells by using CD134 as a binding receptor.

Abstract

The major surface glycoprotein of feline immunodeficiency virus (FIV) specifically binds to a 43-kDa glycoprotein expressed on the surface of a subset of T cells in peripheral blood mononuclear cells and IL-2-dependent T cell lines. Binding to this molecule, in conjunction with CXC chemokine receptor (CXCR) 4, is required for productive infection of these cells by primary isolates of FIV. Here, we demonstrate that the 43-kDa molecule is CD134, a receptor for FIV recently identified independently [Shimojima, M., et al. (2004) Science 303, 1192-1195]. Furthermore, we show that CD134 is specifically up-regulated on CD4+ T cells that have been activated by treatment with IL-2 and Con A. CD8+ T cells remained negative for CD134 expression regardless of the activation state. Binding of the FIV major surface glycoprotein on activated CD4+ T cells was observed through direct interaction with CD134 whereas, on activated CD8+ T cells, the binding was CD134-independent and mediated by CXCR4 and, to a lesser extent, heparan sulfate proteoglycans. However, this CD134-independent interaction was not sufficient to render CD8+ T cells permissive to FIV infection, as FIV replicated primarily in activated CD4+ T cells and not in cells negative for CD134 expression. Altogether, our results substantiate that CD134 acts as a primary binding receptor for FIV and explain the specific targeting and depletion of the CD4+ T cell population observed during the course of infection independent of the use of CD4 as a binding receptor/coreceptor.

• Authors: Aymeric de Parseval, Udayan Chatterji, Peiqing Sun, John H Elder
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 101 Issue 35 Pg. 13044-9 (Aug 31 2004) ISSN: 0027-8424 [Print] United States
• PMID: 15326292 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2004 The National Academy of Sciencs of the USA

Chemical References

• Antibodies
• Receptors, OX40
• Receptors, Tumor Necrosis Factor
• Viral Envelope Proteins

Topics

• Animals
• Antibodies (immunology)
• CD4-Positive T-Lymphocytes (metabolism)
• Cats
• Flow Cytometry
• Immunodeficiency Virus, Feline (metabolism, pathogenicity)
• Receptors, OX40
• Receptors, Tumor Necrosis Factor (immunology, metabolism)
• Viral Envelope Proteins (metabolism)