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

Bridget Sanford; Yan Li; Connor J. Maly; Christian J. Madson; Han Chen; You Zhou; Michael Belshan

doi:10.1016/j.virol.2014.08.017

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

Bridget Sanford, Yan Li, Connor J. Maly, Christian J. Madson, Han Chen, You Zhou, Michael Belshan

Department of Medical Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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 (MAΔ96-120) 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, MAΔ96-120 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.

Original language	English (US)
Pages (from-to)	293-302
Number of pages	10
Journal	Virology
Volume	468
DOIs	https://doi.org/10.1016/j.virol.2014.08.017
State	Published - Nov 1 2014

All Science Journal Classification (ASJC) codes

Virology

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10.1016/j.virol.2014.08.017

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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 (MAΔ96-120) 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, MAΔ96-120 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.",

author = "Bridget Sanford and Yan Li and Maly, {Connor J.} and Madson, {Christian J.} and Han Chen and You Zhou and Michael Belshan",

note = "Funding Information: The authors wish to thank Lee Ratner for the anti-MA and anti-Gag polyclonal antisera and the Creighton University Integrated Biomedical Imaging Core Facility for help with the confocal microscopy. The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: HIV immunoglobulin; HIV-1 gp41 hybridoma (Chessie 8) from George K. Lewis; and pGag-EGFP from Marilyn D. Resh and George Pavlakis. This work was funded by the United States National Institutes of Health , awards GM103509 (the Nebraska Center for Virology) and AI080348 to MB.",

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doi = "10.1016/j.virol.2014.08.017",

language = "English (US)",

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AU - Sanford, Bridget

AU - Li, Yan

AU - Maly, Connor J.

AU - Madson, Christian J.

AU - Chen, Han

AU - Zhou, You

AU - Belshan, Michael

N1 - Funding Information: The authors wish to thank Lee Ratner for the anti-MA and anti-Gag polyclonal antisera and the Creighton University Integrated Biomedical Imaging Core Facility for help with the confocal microscopy. The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: HIV immunoglobulin; HIV-1 gp41 hybridoma (Chessie 8) from George K. Lewis; and pGag-EGFP from Marilyn D. Resh and George Pavlakis. This work was funded by the United States National Institutes of Health , awards GM103509 (the Nebraska Center for Virology) and AI080348 to MB.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - 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 (MAΔ96-120) 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, MAΔ96-120 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.

AB - 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 (MAΔ96-120) 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, MAΔ96-120 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.

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

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