The inhibition of HIV expression in vitro by a cocktail of the
beta-chemokines MIP-1alpha,
MIP-1beta and
RANTES provided the initial evidence that HIV utilizes
chemokine receptors as co-receptors for
infection of cells. Bovine immunodeficiency virus (BIV), a lentivirus, infects a wide variety of leukocyte populations, but the cellular receptor(s) utilized by this virus for
infection of cells is not known. The purpose of this study was to determine whether
MIP-1alpha,
MIP-1beta and
RANTES affect BIV expression in vitro, as a prelude to identifying the cellular receptors utilized by this virus. Fetal bovine lung (FBL) cells were pretreated with serial dilutions of a cocktail of the
chemokines, and then the cells were infected with BIV. Virus expression in these cells was determined by counting the syncytia that had developed in the cultures by five days after
infection. A significant decrease in syncytium formation, corresponding to increasing concentrations of the
chemokines, was the result. Reacting the
chemokines with
chemokine-specific
neutralizing antibodies prior to treatment of the cells neutralized the effect of the
chemokines on virus replication in a dose-dependent manner, restoring viral expression to a level similar to that of untreated cells. The presence of a CCR5 homologue on the surface of FBL cells was confirmed using an anti-CCR5
monoclonal antibody and FACS analysis. Collectively, these data provide preliminary evidence that BIV may utilize the
CCR5 receptor for
infection of cells in vitro, but additional studies are necessary to confirm this.