title: Targeting the Early Step of Building Block Organization in Viral Capsid Assembly.
abstract: Viral assembly, similar to other self-organizing protein systems, relies upon early building blocks, which associate into the late supramolecular structures. An initial and crucial event during HIV-1 core assembly is the dimerization of the capsid protein C-terminal domain, which stabilizes the viral capsid lattice. Thus, monitoring and manipulating this stage is desirable both from mechanistic as well as clinical perspectives. Here, we developed a fluorescent-based method for the detection and visualization of these early capsid interactions. We detected strong dimeric interactions, which were influenced by mutations in the capsid protein. We utilized this assay for potential assembly inhibitors screening, which resulted in the identification of a leading compound that hinders the assembly of capsid protein in vitro. Moreover, a derivative of the compound impaired virus production and infectivity in cell cultures. These findings demonstrate that the described assay efficiently detects the very first association events in HIV-1 capsid formation and emphasize the significance of targeting early intermolecular interactions.
authors.affiliation: †Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Lampel
authors.affiliation: †Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Bram
authors.affiliation: †Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Ezer
authors.affiliation: †Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ronit
authors.initials: R
authors.lastname: Shaltiel-Kario
authors.affiliation: ‡Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, United States.
authors.forename: Jamil S
authors.initials: JS
authors.lastname: Saad
authors.affiliation: §Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Eran
authors.initials: E
authors.lastname: Bacharach
authors.affiliation: †Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.|∥Department of Materials Science and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Gazit
mesh_terms: D002213:Capsid / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D036022:Capsid Proteins / Q000378:metabolism* / Q000648:ultrastructure; D002460:Cell Line; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D008826:Microbial Sensitivity Tests; D008856:Microscopy, Fluorescence; D055503:Protein Multimerization; D013050:Spectrometry, Fluorescence; D019065:Virus Assembly / Q000187:drug effects
chemical_list: D036022:Capsid Proteins