title: 3-hydroxyphthalic anhydride-modified human serum albumin as a microbicide candidate against HIV type 1 entry by targeting both viral envelope glycoprotein gp120 and cellular receptor CD4.
abstract: 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. 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 enzyme-linked immunosorbent assay (ELISA) and flow cytometry, while binding of HP-HSA to the coreceptor CXCR4 or CCR5 was detected by cell-based ELISA. 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. These results suggest that HP-HSA inhibits HIV-1 entry into the target cell by interacting with viral Env gp120 and/or the cellular CD4 receptor, making it a promising microbicide candidate for preventing HIV-1 sexual transmission.
authors.affiliation: 1 Center for Clinical Laboratory, Zhujiang Hospital, Southern Medical University , Guangzhou, China .
authors.forename: Minmin
authors.initials: M
authors.lastname: Li
authors.forename: Jiangman
authors.initials: J
authors.lastname: Duan
authors.forename: Jiayin
authors.initials: J
authors.lastname: Qiu
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Che
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D023581:HIV Fusion Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D010796:Phthalic Anhydrides / Q000494:pharmacology*; D011485:Protein Binding; D012709:Serum Albumin / Q000494:pharmacology*; D000075462:Serum Albumin, Human; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: C422455:ALB protein, human; D000890:Anti-Infective Agents; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120; D023581:HIV Fusion Inhibitors; D010796:Phthalic Anhydrides; D012709:Serum Albumin; C514793:gp120 protein, Human immunodeficiency virus 1; C478070:3-hydroxyphthalic anhydride; D000075462:Serum Albumin, Human