Article ID Journal Published Year Pages File Type
2510282 Antiviral Research 2011 9 Pages PDF
Abstract

Bone marrow stromal cell antigen 2 (BST-2, also known as Tetherin) inhibits HIV-1 release and thereby severely impairs viral replication. HIV-1 accessory protein Vpu induces the down-regulation of cell surface BST-2, and counteracts the antiviral function of BST-2. Blocking Vpu-mediated down-regulation of cell surface BST-2 is viewed as a new opportunity for developing anti-HIV drugs. In this study, we have developed a high-throughput cell-based ELISA to identify small molecules that antagonize HIV-1 Vpu function and consequently inhibit HIV-1 replication through rescuing the antiviral activity of host BST-2. This cell-ELISA shows an excellent correlation with results obtained by flow cytometry (FACS). Under optimal conditions, a Z′ factor of 0.605 was achieved in a 96-well format. Together, these results demonstrate that this assay can be used to quantify the cell surface level of BST-2 and be adapted to a high-throughput screening for novel anti-HIV compounds.

► Blocking Vpu-mediated down-regulation of cell surface BST-2 is viewed as a new opportunity for developing anti-HIV drugs. ► Establishment of the first high-throughput assay to screen novel anti-HIV drug targeting BST-2 down-regulation by Vpu. ► The simple and economic assay shows an excellent correlation with with results obtained by flow cytometry (FACS). ► Provide a proof-of-concept of implementing the same strategy to develop new drugs against other viruses sensitive to BST-2.

Related Topics
Life Sciences Immunology and Microbiology Virology
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