Comparative study on the effect of human BST-2/Tetherin on HIV-1 release in cells of various species

In this study, we first demonstrate that endogenous hBST-2 is predominantly expressed on the plasma membrane of a human T cell line, MT-4 cells, and that Vpu-deficient HIV-1 was less efficiently released than wild-type HIV-1 from MT-4 cells. In addition, surface hBST-2 was rapidly down-regulated in wild-type but not Vpu-deficient HIV-1-infected cells. This is a direct insight showing that provirus-encoded Vpu has the potential to down-regulate endogenous hBST-2 from the surface of HIV-1-infected T cells. Corresponding to previous reports, the aforementioned findings suggested that hBST-2 has the potential to suppress the release of Vpu-deficient HIV-1. However, the molecular mechanism(s) for tethering HIV-1 particles by hBST-2 remains unclear, and we speculated about the requirement for cellular co-factor(s) to trigger or assist its tethering ability. To explore this possibility, we utilize several cell lines derived from various species including human, AGM, dog, cat, rabbit, pig, mink, potoroo, and quail. We found that ectopic hBST-2 was efficiently expressed on the surface of all analyzed cells, and its expression suppressed the release of viral particles in a dose-dependent manner. These findings suggest that hBST-2 can tether HIV-1 particles without the need of additional co-factor(s) that may be expressed exclusively in primates, and thus, hBST-2 can also exert its function in many cells derived from a broad range of species. Interestingly, the suppressive effect of hBST-2 on HIV-1 release in Vero cells was much less pronounced than in the other examined cells despite the augmented surface expression of ectopic hBST-2 on Vero cells. Taken together, our findings suggest the existence of certain cell types in which hBST-2 cannot efficiently exert its inhibitory effect on virus release. The cell type-specific effect of hBST-2 may be critical to elucidate the mechanism of BST-2-dependent suppression of virus release