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3-Hydroxyphthalic anhydride-modified human serum albumin as a microbicide candidate against HIV-1 entry by targeting both viral envelope glycoprotein gp120 and cellular receptor CD4.

AIDS Res Hum Retroviruses. 2013 May 27;

Authors: Li M, Duan J, Qiu J, Yu F, Che X, Jiang S, Li L


Objectives: We previously reported that 3-hydroxyphthalic anhydride-modified human serum albumin (HP-HSA) as an anti-HIV microbicide could potently inhibit infection by a broad spectrum of HIV-1 strains; however, its mechanism of action is still elusive. Here, we aimed to identify the target(s) of HP-HSA. Methods: HIV-1 envelope glycoprotein (Env)-mediated cell-cell fusion assays were conducted using noninfectious CHO-WT cells or infectious HIV-1IIIB-infected H9 cells as effector cells and MT-2 as target cells. The cell-to-cell transmission and single-round HIV-1 infection assays were performed by measuring luciferase activity. Binding of HP-HSA to CD4 or gp120 was determined by ELISA and flow cytometry, while binding of HP-HSA to the coreceptor CXCR4 or CCR5 was detected by cell-based ELISA. Results: HP-HSA strongly inhibited HIV-1 Env-mediated cell-cell fusion and blocked infection by HIV-1 pseudoviruses bearing Env of HIV-1HXB2 (X4 strain) or HIV-1SF162 (R5 strain). HP-HSA was also effective in blocking HIV-1BaL transmission from infected to uninfected cells. HP-HSA could strongly bind to HIV-1 Env gp120 and cellular receptor CD4. Conclusions: These results suggest that HP-HSA inhibits HIV-1 entry into the target cell by interacting with viral Env gp120 and/or cellular CD4 receptor, making it a promising microbicide candidate for preventing HIV-1 sexual transmission.

PMID: 23711095 [PubMed - as supplied by publisher]