title: 3-Hydroxyphthalic anhydride-modified human serum albumin as a microbicide candidate inhibits HIV infection by blocking viral entry.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Pharmaceutical Sciences,  Southern Medical University, Guangzhou 510515,  China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Jiayin
authors.initials: J
authors.lastname: Qiu
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Shengli
authors.initials: S
authors.lastname: An
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Qiao
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Shuwen
authors.initials: S
authors.lastname: Liu
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000821:virology; D005260:Female; D023581:HIV Fusion Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D010796:Phthalic Anhydrides / Q000494:pharmacology*; 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; D023581:HIV Fusion Inhibitors; D010796:Phthalic Anhydrides; D012709:Serum Albumin; C478070:3-hydroxyphthalic anhydride; D007371:Interferon-gamma; D000075462:Serum Albumin, Human