---
APC_amount: 12348 EUR
OA_place: publisher
OA_type: hybrid
_id: '17884'
abstract:
- lang: eng
  text: Human T cell leukemia virus type 1 (HTLV-1) immature particles differ in morphology
    from other retroviruses, suggesting a distinct way of assembly. Here we report
    the results of cryo-electron tomography studies of HTLV-1 virus-like particles
    assembled in vitro, as well as derived from cells. This work shows that HTLV-1
    uses a distinct mechanism of Gag–Gag interactions to form the immature viral lattice.
    Analysis of high-resolution structural information from immature capsid (CA) tubular
    arrays reveals that the primary stabilizing component in HTLV-1 is the N-terminal
    domain of CA. Mutagenesis analysis supports this observation. This distinguishes
    HTLV-1 from other retroviruses, in which the stabilization is provided primarily
    by the C-terminal domain of CA. These results provide structural details of the
    quaternary arrangement of Gag for an immature deltaretrovirus and this helps explain
    why HTLV-1 particles are morphologically distinct.
acknowledged_ssus:
- _id: ScienComp
- _id: LifeSc
- _id: EM-Fac
acknowledgement: This work was funded by the Institute of Science and Technology Austria
  (ISTA) and the Austrian Science Fund (grant P31445 to F.K.M.S.). Access to high-resolution
  cryo-ET data acquisition at European Molecular Biology Laboratory (EMBL) Heidelberg
  was supported through the EMBL cryo-EM platform. We thank V.-V. Hodirnau at ISTA
  and W. Hagen and F. Weis at EMBL Heidelberg for support in cryo-ET data acquisition.
  This research was also supported by the scientific service units of ISTA through
  resources provided by Scientific Computing, the Life Science Facility, and the EM
  Facility. L.M.M. was supported by National Institutes of Health grants R01 GM151775
  and R21 DE032878 and by the University of Minnesota Masonic Cancer Center. D.P.
  was supported by the DOC doctoral fellowship program of the Austrian Academy of
  Sciences. R.A.D was supported by the National Institute of Allergy and Infectious
  Diseases (grant R01AI147890). The funders had no role in study design, data collection
  and analysis, decision to publish or preparation of the manuscript. Specifically,
  we also want to thank A. Schlögl for computational support and J. Hansen and V.
  Vogt for critical comments on the manuscript. We also thank the other members of
  the Schur lab for helpful discussions and experimental advice.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Martin
  full_name: Obr, Martin
  id: 4741CA5A-F248-11E8-B48F-1D18A9856A87
  last_name: Obr
  orcid: 0000-0003-1756-6564
- first_name: Mathias
  full_name: Percipalle, Mathias
  id: 4986e21c-eb97-11eb-a6c2-a4ef0b629971
  last_name: Percipalle
- first_name: Darya
  full_name: Chernikova, Darya
  id: 7dbaf460-fa9e-11eb-b0ca-bc7c7ff21ad0
  last_name: Chernikova
- first_name: Huixin
  full_name: Yang, Huixin
  last_name: Yang
- first_name: Andreas
  full_name: Thader, Andreas
  id: 3A18A7B8-F248-11E8-B48F-1D18A9856A87
  last_name: Thader
- first_name: Gergely
  full_name: Pinke, Gergely
  id: 4D5303E6-F248-11E8-B48F-1D18A9856A87
  last_name: Pinke
- first_name: Dario J
  full_name: Porley, Dario J
  id: 2FD6EA6C-F248-11E8-B48F-1D18A9856A87
  last_name: Porley
- first_name: Louis M.
  full_name: Mansky, Louis M.
  last_name: Mansky
- first_name: Robert A.
  full_name: Dick, Robert A.
  last_name: Dick
- first_name: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
citation:
  ama: Obr M, Percipalle M, Chernikova D, et al. Distinct stabilization of the human
    T cell leukemia virus type 1 immature Gag lattice. <i>Nature Structural &#38;
    Molecular Biology</i>. 2025;32:268-276. doi:<a href="https://doi.org/10.1038/s41594-024-01390-8">10.1038/s41594-024-01390-8</a>
  apa: Obr, M., Percipalle, M., Chernikova, D., Yang, H., Thader, A., Pinke, G., …
    Schur, F. K. (2025). Distinct stabilization of the human T cell leukemia virus
    type 1 immature Gag lattice. <i>Nature Structural &#38; Molecular Biology</i>.
    Springer Nature. <a href="https://doi.org/10.1038/s41594-024-01390-8">https://doi.org/10.1038/s41594-024-01390-8</a>
  chicago: Obr, Martin, Mathias Percipalle, Darya Chernikova, Huixin Yang, Andreas
    Thader, Gergely Pinke, Darío Porley Esteves, Louis M. Mansky, Robert A. Dick,
    and Florian KM Schur. “Distinct Stabilization of the Human T Cell Leukemia Virus
    Type 1 Immature Gag Lattice.” <i>Nature Structural &#38; Molecular Biology</i>.
    Springer Nature, 2025. <a href="https://doi.org/10.1038/s41594-024-01390-8">https://doi.org/10.1038/s41594-024-01390-8</a>.
  ieee: M. Obr <i>et al.</i>, “Distinct stabilization of the human T cell leukemia
    virus type 1 immature Gag lattice,” <i>Nature Structural &#38; Molecular Biology</i>,
    vol. 32. Springer Nature, pp. 268–276, 2025.
  ista: Obr M, Percipalle M, Chernikova D, Yang H, Thader A, Pinke G, Porley Esteves
    D, Mansky LM, Dick RA, Schur FK. 2025. Distinct stabilization of the human T cell
    leukemia virus type 1 immature Gag lattice. Nature Structural &#38; Molecular
    Biology. 32, 268–276.
  mla: Obr, Martin, et al. “Distinct Stabilization of the Human T Cell Leukemia Virus
    Type 1 Immature Gag Lattice.” <i>Nature Structural &#38; Molecular Biology</i>,
    vol. 32, Springer Nature, 2025, pp. 268–76, doi:<a href="https://doi.org/10.1038/s41594-024-01390-8">10.1038/s41594-024-01390-8</a>.
  short: M. Obr, M. Percipalle, D. Chernikova, H. Yang, A. Thader, G. Pinke, D. Porley
    Esteves, L.M. Mansky, R.A. Dick, F.K. Schur, Nature Structural &#38; Molecular
    Biology 32 (2025) 268–276.
corr_author: '1'
date_created: 2024-09-08T10:29:06Z
date_published: 2025-02-01T00:00:00Z
date_updated: 2026-03-16T12:55:18Z
day: '01'
ddc:
- '570'
department:
- _id: FlSc
- _id: LeSa
doi: 10.1038/s41594-024-01390-8
external_id:
  isi:
  - '001306564000001'
  oaworkid:
  - W4402316284
  pmid:
  - '39242978'
file:
- access_level: open_access
  checksum: c641ad94afb28917b20425db676fc3ee
  content_type: application/pdf
  creator: dernst
  date_created: 2025-04-23T07:02:33Z
  date_updated: 2025-04-23T07:02:33Z
  file_id: '19608'
  file_name: 2025_NatureStrucBio_Obr.pdf
  file_size: 13724041
  relation: main_file
  success: 1
file_date_updated: 2025-04-23T07:02:33Z
has_accepted_license: '1'
intvolume: '        32'
isi: 1
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
oaworkid: 1
page: 268-276
pmid: 1
project:
- _id: 26736D6A-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: P31445
  name: Structural conservation and diversity in retroviral capsid
- _id: 9B9C98E0-BA93-11EA-9121-9846C619BF3A
  grant_number: '25762'
  name: Structural characterization of spumavirus capsid assemblies to understand
    conserved Ortervirales assembly mechanisms
publication: Nature Structural & Molecular Biology
publication_identifier:
  eissn:
  - 1545-9985
  issn:
  - 1545-9993
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Distinct stabilization of the human T cell leukemia virus type 1 immature Gag
  lattice
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 32
year: '2025'
...
---
OA_place: publisher
_id: '18101'
abstract:
- lang: eng
  text: "The Retroviridae family consists of two sub-families, the Orthoretrovirinae
    and the\r\nSpumaretrovirinae. The Orthoretroviruses contain important human pathogens,
    such as the\r\nhuman immunodeficiency virus 1 (HIV-1). They also harbor other
    retrovirus species which\r\nare regularly used as model systems to study the retroviral
    life cycle. The main structural\r\ncomponent of the retroviruses, is the Gag protein
    and its truncation derivatives occurring\r\nduring viral maturation. Orthoretroviral
    Gag assemblies have been extensively studied to\r\nunderstand the interactions
    that confer stability and morphology to viral particles.\r\nThe Spumaretrovirinae
    subfamily represent an early diverging branch of the Retroviridae.\r\nIts members,
    the Foamy viruses (FV), share most of the conventional features found in\r\nretroviruses.
    However, they also possess multiple characteristics that make them unique. In\r\nparticular,
    FV Gag does not get extensively cleaved as in orthoretroviruses. Hence, the Gag\r\narchitecture
    deviates from the canonical domain arrangement in FV. They also exhibit a\r\npeculiar
    particle morphology, having no apparent immature state and a seemingly\r\nicosahedral
    mature particle. Due to this, many fundamental questions on FV structural\r\nassembly
    mechanisms remain open. To answer these questions, was the main focus of this\r\nthesis.\r\nMainly,
    it is not known how FV assemble their core in a virus particle and what are the\r\nimportant
    assembly interaction sites within said core. What is the minimum assembly\r\ncompetent
    domain of FV Gag? Is there a morphological change in the assembly type of FVGag
    lattices? If so, what is defining these morphological shifts? Finally, it would
    be\r\ninteresting to know what is the evolutionary relationship between FV and
    the rest of the\r\nretrotranscribing elements, from a structural point of view?\r\nTo
    answer these questions, membrane-enveloped mammalian cell-derived FV virus-like\r\nparticles
    (VLPs) were produced. Cryo-electron tomography (cryo-ET) analysis suggested\r\nthese
    FV VLPs do not form a canonical retroviral Gag lattice structure, which is in
    line with\r\nearlier observations. To further evaluate FV Gag assembly competence
    and morphology,\r\nthe first bacterial cell-derived in vitro VLP assembly system
    was designed and optimized.\r\nUsing this system with different truncation variants,
    the minimum assembly competent\r\ndomain of FV Gag was found to be the putative
    CA300-477 domain. Varying VLP\r\nmorphologies were also observed and strongly
    suggested residues upstream of CA300-477\r\nplay a role in morphology determination.
    Finally, a combined cryo-electron microscopy (cryoEM) and cryo-ET approach was
    taken to analyze tubular assemblies from the minimal\r\nassembly competent domain.
    This revealed an unexpectedly unique non-canonical\r\nassembly architecture. Three
    novel lattice stabilizing interfaces were described which\r\nproved to be as unique
    as the lattice arrangement. Comparison to a newly published FV CA\r\ncore structure
    revealed the CA-CA interactions in the atypical assembly do not recapitulate\r\nwhat
    is described for the FV core lattice. However, the new in vitro VLP assembly system\r\nobtained
    in this thesis also provides an exciting opportunity to study still unresolved
    FV\r\nassembly features in a potentially facilitated approach compared to conventional
    methods.\r\nIn summary, this work provided a deeper understanding of the basic
    FV Gag assembly unit,\r\nas well as presenting the first FV Gag-derived in vitro
    VLP assembly system. This system\r\nreveals a novel and unique assembly architecture
    among retroviral in vitro assemblies."
acknowledged_ssus:
- _id: EM-Fac
- _id: LifeSc
- _id: ScienComp
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Dario J
  full_name: Porley, Dario J
  id: 2FD6EA6C-F248-11E8-B48F-1D18A9856A87
  last_name: Porley
citation:
  ama: Porley Esteves D. Structural characterization of spumavirus capsid assemblies.
    2024. doi:<a href="https://doi.org/10.15479/at:ista:18101">10.15479/at:ista:18101</a>
  apa: Porley Esteves, D. (2024). <i>Structural characterization of spumavirus capsid
    assemblies</i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:18101">https://doi.org/10.15479/at:ista:18101</a>
  chicago: Porley Esteves, Darío. “Structural Characterization of Spumavirus Capsid
    Assemblies.” Institute of Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:18101">https://doi.org/10.15479/at:ista:18101</a>.
  ieee: D. Porley Esteves, “Structural characterization of spumavirus capsid assemblies,”
    Institute of Science and Technology Austria, 2024.
  ista: Porley Esteves D. 2024. Structural characterization of spumavirus capsid assemblies.
    Institute of Science and Technology Austria.
  mla: Porley Esteves, Darío. <i>Structural Characterization of Spumavirus Capsid
    Assemblies</i>. Institute of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:18101">10.15479/at:ista:18101</a>.
  short: D. Porley Esteves, Structural Characterization of Spumavirus Capsid Assemblies,
    Institute of Science and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-09-20T10:21:03Z
date_published: 2024-09-26T00:00:00Z
date_updated: 2026-04-07T13:21:01Z
day: '26'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: FlSc
doi: 10.15479/at:ista:18101
ec_funded: 1
file:
- access_level: closed
  checksum: 3b8b0bacfe61112f3852744f3170e468
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: dporley
  date_created: 2024-09-26T13:40:33Z
  date_updated: 2025-03-25T23:30:03Z
  embargo_to: open_access
  file_id: '18149'
  file_name: PhD_thesis_DPorley_final_20240919.docx
  file_size: 14213128
  relation: source_file
- access_level: open_access
  checksum: 6c3a652a8eede874118e11d66a63652f
  content_type: application/pdf
  creator: dporley
  date_created: 2024-09-26T13:41:39Z
  date_updated: 2025-03-25T23:30:03Z
  embargo: 2025-03-25
  file_id: '18150'
  file_name: PhD_thesis_DPorley_final_20240926_pdfa1.pdf
  file_size: 18583031
  relation: main_file
file_date_updated: 2025-03-25T23:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: '131'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 9B9C98E0-BA93-11EA-9121-9846C619BF3A
  grant_number: '25762'
  name: Structural characterization of spumavirus capsid assemblies to understand
    conserved Ortervirales assembly mechanisms
publication_identifier:
  isbn:
  - 978-3-99078-041-1
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Florian KM
  full_name: Schur, Florian KM
  id: 48AD8942-F248-11E8-B48F-1D18A9856A87
  last_name: Schur
  orcid: 0000-0003-4790-8078
title: Structural characterization of spumavirus capsid assemblies
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...