3-Hydroxyphthalic anhydride-modified human serum albumin as a microbicide candidate inhibits HIV infection by blocking viral entry

• Published in: Journal of antimicrobial chemotherapy Vol. 68; no. 3; pp. 573 - 576
• Main Authors: Li, Lin, Qiu, Jiayin, Lu, Lu, An, Shengli, Qiao, Pengyuan, Jiang, Shibo, Liu, Shuwen
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01.03.2013
• Subjects: Anti-Infective Agents - pharmacology; Antimicrobial agents; Antiviral activity; Antiviral agents; Cell growth; Cell Proliferation; Cells, Cultured; Cytotoxicity; Disease transmission; Drug resistance; Enzyme-linked immunosorbent assay; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - virology; Female; gamma -Interferon; HIV; HIV Fusion Inhibitors - pharmacology; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus; Human immunodeficiency virus 1; human serum albumin; Humans; Hypersensitivity; Immunoassay; Immunogenicity; Infection; Infectivity; Interferon; Interferon-gamma - secretion; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - virology; microbicides; Ovalbumin; Peripheral blood mononuclear cells; Phthalic Anhydrides - pharmacology; Serum Albumin - pharmacology; Serum Albumin, Human; Vagina; Virus Internalization - drug effects
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dks458

We recently demonstrated that both 3-hydroxyphthalic anhydride (HP)- and maleic anhydride-modified chicken ovalbumin (OVA) could effectively inhibit HIV-1 infection. But because OVA may cause allergy in some human subjects, here we replaced OVA with human serum albumin (HSA) in designing a new anti-HIV-1 agent, HP-HSA, and then tested its anti-HIV-1 activity and cytotoxicity. The in vitro anti-HIV-1 activities of HP-HSA were detected by measuring p24 production and luciferase activity. The cytotoxicities of HP-HSA on target cells and human vaginal and cervical epithelial cells and the effect of HP-HSA on human peripheral blood mononuclear cell (PBMC) proliferation were evaluated by XTT assay. The effect of HP-HSA on interferon-γ secretion by PBMCs was detected by enzyme-linked immunospot (ELISPOT) assay. We found that HP-HSA exhibited broad and potent antiviral activity against infection by the HIV-1 strains tested, including drug-resistant strains. HP-HSA displayed no or low cytotoxicity on human vaginal and cervical epithelial cells and the cells used for testing HIV-1 infectivity. In addition, HP-HSA had no significant effect on proliferation or interferon-γ secretion by normal or phytohaemagglutinin-stimulated human PBMCs. A time-of-addition assay indicated that HP-HSA was an HIV-1 entry inhibitor. Because of its broad and potent anti-HIV-1 activity, low cytotoxicity and low immunogenicity to humans, HP-HSA has great potential for further development as a microbicide to prevent the sexual transmission of HIV.