Shared usage of the chemokine receptor CXCR4 by primary and laboratory-adapted strains of feline immunodeficiency virus

Strains of the feline immunodeficiency virus (FIV) presently under investig ation exhibit distinct patterns of in vitro tropism, In particular, the ada ptation of FIV for propagation in Crandell feline kidney (CrFK) cells resul ts in the selection of strains capable of forming syncytia,vith cell lines of diverse species origin, The infection of CrFK cells by CrFK-adapted stra ins appears to require the chemokine receptor CXCR4 and is inhibited by its natural ligand, stromal cell-derived factor 1 alpha (SDF-1 alpha). Here ry e found that inhibitors of CXCR4-mediated infection by human immunodeficien cy virus type I (HIV-1), such as the bicyclam AMD3100 and short peptides de rived from the amino-terminal region of SDF-1 alpha, also blocked infection of CrFK by FN. Nevertheless, we observed differences in the ranking order of the peptides as inhibitors of FIV and HIV-1 and showed that such differe nces are related to the species origin of CXCR4 and not that of the viral e nvelope, These results suggest that, although the envelope glycoproteins of FIV and HIV-1 are substantially divergent, FIV and HIV-1 interact with CXC R4 in a highly similar manner, We have also addressed the role of CXCR4 in the life cycle of primary isolates of FIV, Various CXCR4 ligands inhibited infection of feline peripheral blood mononuclear cells (PBMC) by primary FI V isolates in a concentration-dependent manner. These ligands also blocked the viral transduction of feline PBMC by pseudotyped viral particles when i nfection was mediated by the envelope glycoprotein of a primary FIV isolate but not by the G protein of vesicular stomatitis virus, indicating that th ey act at an envelope-mediated step and presumably at viral entry. These fi ndings strongly suggest that primary and CrFK-adapted strains of FIV, despi te disparate in vitro tropisms, share usage of CXCR4.