title: Deletions in the fifth alpha helix of HIV-1 matrix block virus release.
abstract: The matrix (MA) protein of HIV-1 is the N-terminal component of the Gag structural protein and is critical for the early and late stages of viral replication. MA contains five α-helices (α1-α5). Deletions in the N-terminus of α5 as small as three amino acids impaired virus release. Electron microscopy of one deletion mutant (MA∆96-120) showed that its particles were tethered to the surface of cells by membranous stalks. Immunoblots indicated all mutants were processed completely, but mutants with large deletions had alternative processing intermediates. Consistent with the EM data, MA∆96-120 retained membrane association and multimerization capability. Co-expression of this mutant inhibited wild type particle release. Alanine scanning mutation in this region did not affect virus release, although the progeny virions were poorly infectious. Combined, these data demonstrate that structural ablation of the α5 of MA inhibits virus release.
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA.
authors.forename: Bridget
authors.initials: B
authors.lastname: Sanford
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA.
authors.forename: Connor J
authors.initials: CJ
authors.lastname: Maly
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Madson
authors.affiliation: Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Chen
authors.affiliation: Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE, USA; Nebraska Center for Virology, Lincoln, NE, USA.
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA; Nebraska Center for Virology, Lincoln, NE, USA. Electronic address: michaelbelshan@creighton.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Belshan
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002462:Cell Membrane; D017353:Gene Deletion; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D057074:Virus Release / Q000235:genetics*
chemical_list: D014763:Viral Matrix Proteins
keywords: Deletion mutagenesis; HIV-1 assembly; HIV-1 budding; Matrix; NEDD4L