The Studies On The Network Of Human Innate ANTI-HIV-1Factors And BST-2

The innate antiviral factors in humans that have been discovered recently not onlyinteract with HIV-1components, but also have broad protein-protein interactions with otherproteins. All these factors form a large network in which some of these proteins with similarstructures and similar functions may form complexes in order to accomplish specific biologicpathways. This study utilized a network building and analyzing software, Cytoscape, to createa network of7proteins (i.e. APOBEC3G, Trim5α, BST-2, CBF-β, Vif, Gag and Vpu) that arerelated to HIV-1, and predicted four putative complexes with Clusterviz plugin. Among theseresults, Vpu and BST-2were shown to have a potential interaction with each other, whichsuggests that further investigation on BST-2is required to elucidate the mechanism of thisinteraction.BST-2is an innate antiviral factor that has been discovered recently and the mechanismby which BST-2inhibits HIV-1virion release still needs much elucidation. This study alsopicked this new antiviral factor from the network for further research. BST-2can "tether"HIV-1virion to the cellular membrane, therefore inhibit its release from the infected cell.HIV-1Vpu can antagonize this effect. This ability of Vpu to antagonize BST-2is speciesspecific. HIV-1Vpu can down-regulate the level of cell surface BST-2in human, while it hasno effect on that in African Green Monkey and Rhesus Monkey. This study harvested theBST-2cDNA from HeLa cells, and then constructed two eukaryotic expression vectors,pEGFP-BST-2and pFC15A-BST-2. BST-2fusion proteins mainly located in the cytoplasmand membrane, and distributed unevenly in293FT cells. Based on the discrepancies in thetransmembrane domain among Human, African Green Monkey and Rhesus Monkey BST-2proteins, six BST-2mutants were constructed.