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Cited by 336HIV Research and TreatmentT-cell and Retrovirus StudiesHIV/AIDS drug development and treatment

Sequential Steps in Human Immunodeficiency Virus Particle Maturation Revealed by Alterations of Individual Gag Polyprotein Cleavage Sites

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Wiegers, Klaus, Rutter, Gabriel, Kottler, Hubert, Tessmer, Uwe, Hohenberg, Heinz, Kräusslich, Hans-Georg·1998·Journal of Virology
DOI 10.1128/jvi.72.4.2846-2854.1998PMC PMC109729
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Abstract

Retroviruses are produced as immature particles containing structural polyproteins, which are subsequently cleaved by the viral proteinase (PR). Extracellular maturation leads to condensation of the spherical core to a capsid shell formed by the capsid (CA) protein, which encases the genomic RNA complexed with nucleocapsid (NC) proteins. CA and NC are separated by a short spacer peptide (spacer peptide 1 [SP1]) on the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein and released by sequential PR-mediated cleavages. To assess the role of individual cleavages in maturation, we constructed point mutations abolishing cleavage at these sites, either alone or in combination. When all three sites between CA and NC were mutated, immature particles containing stable CA-NC were observed, with no apparent effect on other cleavages. Delayed maturation with irregular morphology of the ribonucleoprotein core was observed when cleavage of SP1 from NC was prevented. Blocking the release of SP1 from CA, on the other hand, yielded normal condensation of the ribonucleoprotein core but prevented capsid condensation. A thin, electron-dense layer near the viral membrane was observed in this case, and mutant capsids were significantly less stable against detergent treatment than wild-type HIV-1. We suggest that HIV maturation is a sequential process controlled by the rate of cleavage at individual sites. Initial rapid cleavage at the C terminus of SP1 releases the RNA-binding NC protein and leads to condensation of the ribonucleoprotein core. Subsequently, CA is separated from the membrane by cleavage between the matrix protein and CA, and late release of SP1 from CA is required for capsid condensation.

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Crossref · 10.1128/jvi.72.4.2846-2854.1998

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  • When Gag-Pol is unincorporated from assembly sites, protease activity is reduced, virus release is impaired, and budding virions have thicker unprocessed Gag shell.

    “When Gag-pol is unincorporated from assembly sites, protease activity is reduced, virus release is impaired and budding virions are marked by a thicker Gag shell that has gone unprocessed [46].”

    From Budding of a Retrovirus: Some Assemblies Required (2020) · cites this paper as [46]

  • Tight control of proteolytic cleavages at different sites is required for successful maturation.

    “Tight control of proteolytic cleavages at different sites is required for successful maturation, and the process is a major target of antiretroviral drugs.”

    From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [64]

  • Abolishing or altering the rates of cleavage at individual sites leads to maturation and core morphology defects and loss of infectivity.

    “Abolishing or altering the rates of cleavage at individual sites leads to maturation and core morphology defects [64][65][66][67] and loss of infectivity”

    From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [64]

  • Cleavage upstream of CA and downstream of SP1 leads to disruption of the immature lattice, while cleavage between CA and SP1 is additionally required to assemble the mature lattice.

    “Cleavage upstream of CA and downstream of SP1 leads to disruption of the immature lattice, while cleavage between CA and SP1 is additionally required to assemble the mature lattice”

    From Retrovirus maturation-an extraordinary structural transformation (2016) · cites this paper as [64]

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Authors
Wiegers, K., Rutter, G., Kottler, H., Tessmer, U., Hohenberg, H., & Kräusslich, H.-G.
Affiliations
  • Leibniz Institute of Virology (LIV) (DE)
  • <!--label omitted: 1-->Heinrich-Pette-Institut, D-20251 Hamburg,1 and
  • German Cancer Research Center (DE)
Venue
Journal of Virology
Publisher
American Society for Microbiology
Published
1998-04
Volume
72
Issue
4
Pages
2846-2854
ISSN
  • 0022-538X (ISSN-L)
  • 1098-5514
DOI
10.1128/jvi.72.4.2846-2854.1998
PMC
PMC109729
OpenAlex
W2169408873
Cited by
336
References
65
Citations by year
2026: 5 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 15 · 2021: 12 · 2020: 12 · 2019: 9 · 2018: 7 · 2017: 11 · 2016: 12 · 2015: 21 · 2014: 11 · 2013: 15 · 2012: 10
FWCI
3.29
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Journal of Virology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
HIV-1, virus maturation, Gag protein, proteolytic cleavage sites, capsid protein, nucleocapsid protein, capsid stability, point mutations, matrix protein
MeSH terms
Amino Acid Sequence, Animals, Binding Sites, Capsid, Cell Line, Cell Line, Transformed, Cloning, Molecular, Detergents, Humans, Molecular Sequence Data, Protein Processing, Post-Translational, Proteins, Virion, HIV-1, Gene Products, gag, HIV Protease, Point Mutation, Octoxynol, Virus Assembly, COS Cells

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