title: Hydrophobic Nanoparticles Reduce the β-Sheet Content of SEVI Amyloid Fibrils and Inhibit SEVI-Enhanced HIV Infectivity.
abstract: Semen-derived enhancer of virus infection (SEVI) fibrils are naturally abundant amyloid aggregates found in semen that facilitate viral attachment and internalization of human immunodeficiency virus (HIV) in cells, thereby increasing the probability of infection. Mature SEVI fibrils are composed of aggregated peptides exhibiting high β-sheet secondary structural characteristics. Herein, we show that polymers containing hydrophobic side chains can interact with SEVI and reduce its β-sheet content by ∼45% compared with the β-sheet content of SEVI in the presence of polymers with hydrophilic side chains, as estimated by polarization modulation-infrared reflectance absorption spectroscopy measurements. A nanoparticle (NP) formulation of this hydrophobic polymer reduced SEVI-mediated HIV infection in TMZ-bl cells by 60% compared with the control treatment. Although these NPs lacked specific amyloid-targeting groups, thus requiring high concentrations to observe biological activity, the use of hydrophobic interactions to alter the secondary structure of amyloids represents a useful approach to neutralizing the SEVI function. These results could, therefore, have general implications in the design of novel materials that can modify the activity of amyloids associated with a variety of other neurological and systemic diseases.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Sheik
authors.affiliation: Department of Microbiology and Immunology, University of Rochester , Rochester, New York 14642, United States.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Chamberlain
authors.affiliation: Department of Microbiology and Immunology, University of Rochester , Rochester, New York 14642, United States.
authors.forename: Lauren
authors.initials: L
authors.lastname: Brooks
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Melissa
authors.initials: M
authors.lastname: Clark
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Geoffray
authors.initials: G
authors.lastname: Leriche
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Clifford P
authors.identifier: 0000-0003-2186-488X
authors.initials: CP
authors.lastname: Kubiak
authors.affiliation: Department of Microbiology and Immunology, University of Rochester , Rochester, New York 14642, United States.
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego , 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
authors.forename: Jerry
authors.identifier: 0000-0002-8423-7376
authors.initials: J
authors.lastname: Yang
mesh_terms: D000682:Amyloid; D015658:HIV Infections; D053758:Nanoparticles; D000072757:Protein Conformation, beta-Strand; D012661:Semen
chemical_list: D000682:Amyloid