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Title: Deletions in the fifth alpha helix of HIV-1 matrix block virus release

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. - Highlights: • Deletions were identified in the C-terminus of matrix that block virus release. • These deletion mutants still multimerized and associated with membranes. • TEM showed the mutant particles were tethered to the cell surface. • Amino acid mutagenesis of the region did not affect release. • The data suggests that disruption of matrix structure blocks virus release.
Authors:
; ; ;  [1] ;  [2] ;  [2] ;  [3] ;  [1] ;  [3]
  1. Department of Medical Microbiology and Immunology, Creighton University, 2500 California Plaza, Omaha, NE 68178 (United States)
  2. Center for Biotechnology, University of Nebraska-Lincoln, Lincoln, NE (United States)
  3. (United States)
Publication Date:
OSTI Identifier:
22435068
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 468-470; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ABLATION; AIDS VIRUS; ALANINES; MEMBRANES; MUTAGENESIS; MUTANTS; PARTICLES; PROGENY; PROTEINS; SURFACES; TRANSMISSION ELECTRON MICROSCOPY