title: Effects of UVA irradiation, aryl azides, and reactive oxygen species on the orthogonal inactivation of the human immunodeficiency virus (HIV-1).
abstract: Previously we reported that hydrophobic aryl azides partition into hydrophobic regions of the viral membrane of enveloped viruses and inactivate the virus upon UVA irradiation for 2 min. Prolonged irradiation (15 min) resulted in viral protein aggregation as visualized via Western blot analysis, due to reactive oxygen species (ROS) formation, with preservation of the surface antigenic epitopes. Herein, we demonstrate that these aggregates show detergent resistance and that this property may be useful towards the creation of a novel orthogonal virus inactivation strategy for use in preparing experimental vaccines. When ROS-modified HIV virus preparations were treated with 1% Triton X-100, there was an increase in the percent of viral proteins (gp41, p24) in the viral pellet after ultracentrifugation through sucrose. Transmission electron microscopy (TEM) of these detergent-resistant pellets shows some recognizable virus fragments, and immunoprecipitation studies of the gp41 aggregates suggest the aggregation is covalent in nature, involving short-range interactions.
authors: Center for Cancer Research Nanobiology Program, National Cancer Institute Frederick, Frederick, MD 21702, USA.
authors: Julie M
authors: JM
authors: Belanger
authors: Yossef
authors: Y
authors: Raviv
authors: Mathias
authors: M
authors: Viard
authors: M Jason
authors: MJ
authors: de la Cruz
authors: Kunio
authors: K
authors: Nagashima
authors: Robert
authors: R
authors: Blumenthal
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D001386:Azides / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000528:radiation effects*; D009500:Neutralization Tests; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D012995:Solubility; D014466:Ultraviolet Rays; D038301:Virus Inactivation
chemical_list: D019380:Anti-HIV Agents; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D001386:Azides; D017382:Reactive Oxygen Species