Presentation_1_3-Hydroxyphthalic Anhydride- Modified Rabbit Anti-PAP IgG as a Potential Bifunctional HIV-1 Entry Inhibitor.PDF (171.05 kB)
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Presentation_1_3-Hydroxyphthalic Anhydride- Modified Rabbit Anti-PAP IgG as a Potential Bifunctional HIV-1 Entry Inhibitor.PDF

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posted on 19.06.2018, 04:18 by Xuanxuan Zhang, Jinquan Chen, Fei Yu, Chunyan Wang, Ruxia Ren, Qian Wang, Suiyi Tan, Shibo Jiang, Shuwen Liu, Lin Li

Several studies have reported that amyloid fibrils in human semen formed from a naturally occurring peptide fragment of prostatic acidic phosphatase (PAP248-286), known as semen-derived enhancer of viral infection (SEVI), could dramatically enhance human immunodeficiency virus type 1 (HIV-1) infection. Accordingly, SEVI might serve as a novel target for new antiviral drugs or microbicide candidates for the prevention of sexually transmitted HIV. Theoretically, a special anti-PAP or anti-SEVI antibody could reduce the enhancement of viral infection by blocking the binding of HIV and SEVI fibrils. Here, 3-hydroxyphthalic anhydride modified anti-PAP248-286 antibody, named HP-API, exhibited broad-spectrum and highly effective anti-HIV-1 activities on different subtypes and tropism. By using time-of-addition, cell–cell fusion and a single-cycle HIV-1 infection assays, we demonstrated that HP-API is an HIV-1 entry/fusion inhibitor. Mechanism studies suggest that HP-API inhibited HIV-1 entry/fusion by targeting both HIV-1 gp120 envelop and CD4 receptor on the host cell specifically. It is noteworthy that HP-API abrogated the formation of SEVI fibrils and partially interfered with SEVI-mediated enhancement of HIV-1 infection. Based on these findings, HP-API could be considered a bifunctional HIV-1 entry/fusion inhibitor with high potential.

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