Chen Liang

Publications (2)7.03 Total impact

• Article: Characterization of the interface of the bone marrow stromal cell antigen 2-Vpu protein complex via computational chemistry.

  Jinming Zhou, Zhixin Zhang, Zeyun Mi, Xin Wang, Quan Zhang, Xiaoyu Li, Chen Liang, Shan Cen
  [show abstract] [hide abstract]
  ABSTRACT: Bone marrow stromal cell antigen 2 (BST-2) inhibits the release of enveloped viruses from the cell surface. Various viral counter measures have been discovered, which allow viruses to escape BST-2 restriction. Human immunodeficiency virus type 1 (HIV-1) encodes viral protein U (Vpu) that interacts with BST-2 through their transmembrane domains and causes the downregulation of cell surface BST-2. In this study, we used a computer modeling method to establish a molecular model to investigate the binding interface of the transmembrane domains of BST-2 and Vpu. The model predicts that the interface is composed of Vpu residues I6, A10, A14, A18, V25, and W22 and BST-2 residues L23, I26, V30, I34, V35, L41, I42, and T45. Introduction of mutations that have been previously reported to disrupt the Vpu-BST-2 interaction led to a calculated higher binding free energy (MMGBSA), which supports our molecular model. A pharmacophore was also generated on the basis of this model. Our results provide a precise model that predicts the detailed interaction occurring between the transmembrane domains of Vpu and BST-2 and should facilitate the design of anti-HIV agents that are able to disrupt this interaction.
  Biochemistry 02/2012; 51(6):1288-96. · 3.42 Impact Factor
• Article: High-throughput assay to identify inhibitors of Vpu-mediated down-regulation of cell surface BST-2.

  Quan Zhang, Zhenlong Liu, Zeyun Mi, Xiaoyu Li, Pingping Jia, Jinming Zhou, Xiao Yin, Xuefu You, Liyan Yu, Fei Guo, Jing Ma, Chen Liang, Shan Cen
  [show abstract] [hide abstract]
  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.
  Antiviral research 09/2011; 91(3):321-9. · 3.61 Impact Factor