Differential Utilization of CCR5 Molecules from Three East African Primate Species by the HIV-1 Envelope Glycoprotein
This study reports the cloning, sequencing, and functional characterization of novel simian homologs of CCR5 from three species of primates (Papio anubis anubis; Colobus guereza and Cercopithecus neglectus ) which are indigenous to East Africa. Identity at the amino acid level to human CCR5 was 97% for molecules from all three primate species. Functional characterization of these coreceptors was performed using a sensitive gene reporter-based cell-cell fusion assay. Despite a high degree of sequence similarity, significant differences in the degree of M-tropic HIV envelope-specific fusion generated by individual coreceptor molecules were demonstrated. Remarkably, two simian CCR5 molecules (Colobus guereza and Cercopithecus neglectus) demonstrated an increased efficiency of HIV-mediated fusion as compared with the human CCR5 molecule. These results provide further evidence that simian CCR5 molecules differ in their ability to facilitate HIV-1 entry, and may have bearing on the investigation of new simian models for HIV-1 pathogenesis.