@article{17884,
  abstract     = {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.},
  author       = {Obr, Martin and Percipalle, Mathias and Chernikova, Darya and Yang, Huixin and Thader, Andreas and Pinke, Gergely and Porley, Dario J and Mansky, Louis M. and Dick, Robert A. and Schur, Florian KM},
  issn         = {1545-9985},
  journal      = {Nature Structural & Molecular Biology},
  pages        = {268--276},
  publisher    = {Springer Nature},
  title        = {{Distinct stabilization of the human T cell leukemia virus type 1 immature Gag lattice}},
  doi          = {10.1038/s41594-024-01390-8},
  volume       = {32},
  year         = {2025},
}

@phdthesis{18101,
  abstract     = {The Retroviridae family consists of two sub-families, the Orthoretrovirinae and the
Spumaretrovirinae. The Orthoretroviruses contain important human pathogens, such as the
human immunodeficiency virus 1 (HIV-1). They also harbor other retrovirus species which
are regularly used as model systems to study the retroviral life cycle. The main structural
component of the retroviruses, is the Gag protein and its truncation derivatives occurring
during viral maturation. Orthoretroviral Gag assemblies have been extensively studied to
understand the interactions that confer stability and morphology to viral particles.
The Spumaretrovirinae subfamily represent an early diverging branch of the Retroviridae.
Its members, the Foamy viruses (FV), share most of the conventional features found in
retroviruses. However, they also possess multiple characteristics that make them unique. In
particular, FV Gag does not get extensively cleaved as in orthoretroviruses. Hence, the Gag
architecture deviates from the canonical domain arrangement in FV. They also exhibit a
peculiar particle morphology, having no apparent immature state and a seemingly
icosahedral mature particle. Due to this, many fundamental questions on FV structural
assembly mechanisms remain open. To answer these questions, was the main focus of this
thesis.
Mainly, it is not known how FV assemble their core in a virus particle and what are the
important assembly interaction sites within said core. What is the minimum assembly
competent 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
interesting to know what is the evolutionary relationship between FV and the rest of the
retrotranscribing elements, from a structural point of view?
To answer these questions, membrane-enveloped mammalian cell-derived FV virus-like
particles (VLPs) were produced. Cryo-electron tomography (cryo-ET) analysis suggested
these FV VLPs do not form a canonical retroviral Gag lattice structure, which is in line with
earlier observations. To further evaluate FV Gag assembly competence and morphology,
the first bacterial cell-derived in vitro VLP assembly system was designed and optimized.
Using this system with different truncation variants, the minimum assembly competent
domain of FV Gag was found to be the putative CA300-477 domain. Varying VLP
morphologies were also observed and strongly suggested residues upstream of CA300-477
play 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
assembly competent domain. This revealed an unexpectedly unique non-canonical
assembly architecture. Three novel lattice stabilizing interfaces were described which
proved to be as unique as the lattice arrangement. Comparison to a newly published FV CA
core structure revealed the CA-CA interactions in the atypical assembly do not recapitulate
what is described for the FV core lattice. However, the new in vitro VLP assembly system
obtained in this thesis also provides an exciting opportunity to study still unresolved FV
assembly features in a potentially facilitated approach compared to conventional methods.
In summary, this work provided a deeper understanding of the basic FV Gag assembly unit,
as well as presenting the first FV Gag-derived in vitro VLP assembly system. This system
reveals a novel and unique assembly architecture among retroviral in vitro assemblies.},
  author       = {Porley, Dario J},
  isbn         = {978-3-99078-041-1},
  issn         = {2663-337X},
  pages        = {131},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Structural characterization of spumavirus capsid assemblies}},
  doi          = {10.15479/at:ista:18101},
  year         = {2024},
}