title: Glycosyl Phosphatidylinositol-Anchored C34 Peptide Derived From Human Immunodeficiency Virus Type 1 Gp41 Is a Potent Entry Inhibitor.
abstract: Lipid rafts of the plasma membrane have been shown to be gateways for HIV-1 budding and entry. In nature, many glycosyl-phosphatidylinositol (GPI) anchored proteins are targeted to the lipid rafts. In the present study we constructed two fusion genes, in which C34 peptide or AVF peptide control was genetically linked with a GPI-attachment signal. Recombinant lentiviruses expressing the fusion genes were used to transduce TZM.bl and CEMss-CCR5 cells. Here, we show that with a GPI attachment signal both C34 and AVF are targeted to the lipid rafts through a GPI anchor. GPI-C34, but not GPI-AVF, in transduced TZM.bl cells efficiently blocks the infection of diverse HIV-1 strains of various subtypes. GPI-C34-transduced CEMss-CCR5 cells are totally resistant to HIV-1 infection. Importantly, maximum percentage of inhibition (MPI) by GPI-C34 is comparable to, if not higher than, a very high concentration of soluble C34. Potent blocking by GPI-C34 is likely due to its high local concentration, which allows GPI-C34 to efficiently bind to the prehairpin intermediate and prevent its transition to six helical bundle, thereby interfering with membrane fusion and virus entry. Our findings should have important implications in GPI-anchor-based therapy against HIV-1.
authors.affiliation: The Unit of Anti-Viral Immunity and Genetic Therapy, the Key Laboratory of Molecular Virology and Immunology, the Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Liu
authors.affiliation: The Unit of Anti-Viral Immunity and Genetic Therapy, the Key Laboratory of Molecular Virology and Immunology, the Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Michael
authors.initials: M
authors.lastname: Wen
authors.affiliation: The Unit of Anti-Viral Immunity and Genetic Therapy, the Key Laboratory of Molecular Virology and Immunology, the Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Kimata
authors.affiliation: The Unit of Anti-Viral Immunity and Genetic Therapy, the Key Laboratory of Molecular Virology and Immunology, the Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China. blzhou@sibs.ac.cn.
authors.forename: Paul
authors.initials: P
authors.lastname: Zhou
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism* / Q000494:pharmacology; D057809:HEK293 Cells; D015700:HIV Envelope Protein gp41 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D017261:Glycosylphosphatidylinositols; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; C514787:gp41 protein, Human immunodeficiency virus 1; C407149:peptide C34
keywords: C34 peptide; GPI anchor; Gene delivery; HIV-1; Lipid rafts