Title : The formation of
cysteine-linked
dimers of
BST-2 /
tetherin is important for inhibition of HIV-1 virus release but not for sensitivity to
Vpu
Abstract :
- BACKGROUND: The Human Immunodeficiency virus type 1 ( HIV-1) Vpu protein enhances virus release from infected cells and induces proteasomal degradation of CD4
- Recent work identified BST-2 / CD317 as a host factor that inhibits HIV-1 virus release in a Vpu sensitive manner
- A current working model proposes that BST-2 inhibits virus release by tethering viral particles to the cell surface thereby triggering their subsequent endocytosis
- RESULTS: Here we defined structural properties of BST-2 required for inhibition of virus release and for sensitivity to Vpu
- We found that BST-2 is modified by N-linked glycosylation at two sites in the extracellular domain
- However, N-linked glycosylation was not important for inhibition of HIV-1 virus release nor did it affect surface expression or sensitivity to Vpu
- Rodent BST-2 was previously found to form cysteine-linked dimers
- Analysis of single, double, or triple cysteine mutants revealed that any one of three cysteine residues present in the BST-2 extracellular domain was sufficient for BST-2 dimerization , for inhibition of virus release, and sensitivity to Vpu
- In contrast, BST-2 lacking all three cysteines cysteines in its ectodomain was unable to inhibit release of wild type or Vpu-deficient HIV-1 virions
- This defect was not caused by a gross defect in BST-2 trafficking as the mutant protein was expressed at the cell surface of transfected 293T cells and was down-modulated by Vpu similar to wild type BST-2
- CONCLUSION: While BST-2 glycosylation was functionally irrelevant, formation of cysteine-linked dimers appeared to be important for inhibition of virus release
- However lack of dimerization did not prevent surface expression or Vpu sensitivity of BST-2 , suggesting Vpu sensitivity and inhibition of virus release are separable properties of BST-2