Vpu-mediated tetherin antagonism and degradation are separable functions

Wednesday, October 26, 2011 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center	NCI	VIROL/MICRO-22

Authors

• A Waheed
• N Kuruppu
• K Felton
• E Freed

Abstract

An interferon-inducible cellular protein CD317/BST-2 (also known as tetherin) inhibits the release of a variety of enveloped viruses. The HIV-1 accessory protein Vpu enhances virus particle release by counteracting this restriction factor. The antagonism of human tetherin by Vpu is associated with proteasome-mediated degradation. Our recent studies show that human tetherin is poorly expressed in agm kidney (COS) cells due to proteasomal and lysosomal degradation. Surprisingly, however, Vpu markedly increases tetherin expression in this cell line, apparently by sequestering it in an internal compartment that bears lysosomal markers. Although Vpu stablilizes human tetherin in COS cells, it still counteracts the ability of tetherin to suppress virus release. This enhancement of virus release by Vpu in COS cells is associated with a modest reduction in the cell-surface expression of tetherin, even though the overall expression of tetherin is higher in the presence of Vpu. These studies demonstrate that Vpu-mediated enhancement of HIV-1 release can be uncoupled from Vpu-mediated tetherin degradation in COS cells. Thus COS cells provide a system for the molecular dissection of differential functions of Vpu.

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