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Lin Li, Jiayin Qiu, Lu Lu, Shengli An, Pengyuan Qiao, Shibo Jiang, Shuwen Liu, 3-Hydroxyphthalic anhydride-modified human serum albumin as a microbicide candidate inhibits HIV infection by blocking viral entry, Journal of Antimicrobial Chemotherapy, Volume 68, Issue 3, March 2013, Pages 573–576, https://doi.org/10.1093/jac/dks458
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Abstract
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.
- hiv
- hypersensitivity
- anhydrides
- antiviral agents
- bodily secretions
- chickens
- hiv-1
- interferons
- luciferases
- ovalbumin
- ovum
- phytohemagglutinins
- infections
- enzymes
- serum albumin
- vagina
- leptocytes
- epithelial cells
- hiv infections
- human leukocyte interferon
- cytotoxicity
- pathogenicity
- hiv transmission
- enzyme linked immunospot assay
- peripheral blood mononuclear cell
- hiv-1 infection
- entry of virus into host cell
- immunogenicity