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Cited by 114HIV Research and TreatmentAdvanced Electron Microscopy Techniques and ApplicationsT-cell and Retrovirus Studies

Structural Analysis of HIV-1 Maturation Using Cryo-Electron Tomography

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de Marco, Alex, Müller, Barbara, Glass, Bärbel, Riches, James D., Kräusslich, Hans-Georg, Briggs, John A. G.·2010·PLoS Pathogens
DOI 10.1371/journal.ppat.1001215PMC PMC2999899
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Abstract

HIV-1 buds form infected cells in an immature, non-infectious form. Maturation into an infectious virion requires proteolytic cleavage of the Gag polyprotein at five positions, leading to a dramatic change in virus morphology. Immature virions contain an incomplete spherical shell where Gag is arranged with the N-terminal MA domain adjacent to the membrane, the CA domain adopting a hexameric lattice below the membrane, and beneath this, the NC domain and viral RNA forming a disordered layer. After maturation, NC and RNA are condensed within the particle surrounded by a conical CA core. Little is known about the sequence of structural changes that take place during maturation, however. Here we have used cryo-electron tomography and subtomogram averaging to resolve the structure of the Gag lattice in a panel of viruses containing point mutations abolishing cleavage at individual or multiple Gag cleavage sites. These studies describe the structural intermediates correlating with the ordered processing events that occur during the HIV-1 maturation process. After the first cleavage between SP1 and NC, the condensed NC-RNA may retain a link to the remaining Gag lattice. Initiation of disassembly of the immature Gag lattice requires cleavage to occur on both sides of CA-SP1, while assembly of the mature core also requires cleavage of SP1 from CA.

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  • 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 [66]

    The Discussion (page unavailable) reports that blocking cleavage at particular sites disrupts immature-lattice disassembly or regular mature-core formation. The Introduction (page unavailable) reports severely diminished or abolished infectivity when cleavage is blocked at individual sites, but explicitly excepts NC-SP2; it does not establish that altering the rate at any individual site has all the stated effects. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • 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 [66]

    The Discussion section on cleavage and lattice disassembly says cleavage on both sides of CA-SP1 disassembles the immature lattice. It also says CA-SP1 cleavage is needed to form a closed mature core inside the virion, but explicitly says it is not an absolute requirement for mature CA lattice assembly: mature-like lattices can assemble in vitro without it. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • 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 [66]

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Authors
de Marco, A., Müller, B., Glass, B., Riches, J. D., Kräusslich, H.-G., & Briggs, J. A. G.
Affiliations
  • University Hospital Heidelberg (DE)
  • European Molecular Biology Laboratory (DE)
Corresponding author
Briggs, John A. G.
ORCID
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2010-11-24
Volume
6
Issue
11
Pages
e1001215
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1001215
PMC
PMC2999899
OpenAlex
W1971637353
Cited by
114
References
5
Citations by year
2026: 6 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 8 · 2015: 12 · 2014: 16 · 2013: 9 · 2012: 13
FWCI
3.94
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • Institute for Future Environments; Science & Engineering Faculty
Funders
European Commission
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords
Gag protein, immature virions, structural intermediates, proteolytic processing
MeSH terms
Humans, Models, Molecular, RNA, Viral, Tomography, Virion, HIV-1, HIV Infections, Point Mutation, Protein Structure, Tertiary, gag Gene Products, Human Immunodeficiency Virus, Electron Microscope Tomography

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