[{"oa":1,"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"file":[{"content_type":"application/pdf","date_created":"2025-04-23T07:02:33Z","file_name":"2025_NatureStrucBio_Obr.pdf","success":1,"relation":"main_file","date_updated":"2025-04-23T07:02:33Z","creator":"dernst","access_level":"open_access","file_size":13724041,"checksum":"c641ad94afb28917b20425db676fc3ee","file_id":"19608"}],"type":"journal_article","abstract":[{"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.","lang":"eng"}],"date_created":"2024-09-08T10:29:06Z","quality_controlled":"1","status":"public","corr_author":"1","article_type":"original","year":"2025","doi":"10.1038/s41594-024-01390-8","project":[{"name":"Structural conservation and diversity in retroviral capsid","_id":"26736D6A-B435-11E9-9278-68D0E5697425","grant_number":"P31445","call_identifier":"FWF"},{"name":"Structural characterization of spumavirus capsid assemblies to understand conserved Ortervirales assembly mechanisms","_id":"9B9C98E0-BA93-11EA-9121-9846C619BF3A","grant_number":"25762"}],"author":[{"id":"4741CA5A-F248-11E8-B48F-1D18A9856A87","full_name":"Obr, Martin","first_name":"Martin","last_name":"Obr","orcid":"0000-0003-1756-6564"},{"id":"4986e21c-eb97-11eb-a6c2-a4ef0b629971","full_name":"Percipalle, Mathias","last_name":"Percipalle","first_name":"Mathias"},{"last_name":"Chernikova","first_name":"Darya","id":"7dbaf460-fa9e-11eb-b0ca-bc7c7ff21ad0","full_name":"Chernikova, Darya"},{"last_name":"Yang","first_name":"Huixin","full_name":"Yang, Huixin"},{"full_name":"Thader, Andreas","id":"3A18A7B8-F248-11E8-B48F-1D18A9856A87","first_name":"Andreas","last_name":"Thader"},{"full_name":"Pinke, Gergely","id":"4D5303E6-F248-11E8-B48F-1D18A9856A87","first_name":"Gergely","last_name":"Pinke"},{"id":"2FD6EA6C-F248-11E8-B48F-1D18A9856A87","full_name":"Porley, Dario J","first_name":"Dario J","last_name":"Porley"},{"last_name":"Mansky","first_name":"Louis M.","full_name":"Mansky, Louis M."},{"full_name":"Dick, Robert A.","first_name":"Robert A.","last_name":"Dick"},{"id":"48AD8942-F248-11E8-B48F-1D18A9856A87","full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078","first_name":"Florian KM","last_name":"Schur"}],"scopus_import":"1","page":"268-276","day":"01","month":"02","title":"Distinct stabilization of the human T cell leukemia virus type 1 immature Gag lattice","oaworkid":1,"ddc":["570"],"isi":1,"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.","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"license":"https://creativecommons.org/licenses/by/4.0/","publication":"Nature Structural & Molecular Biology","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2025-04-23T07:02:33Z","intvolume":"        32","oa_version":"Published Version","date_published":"2025-02-01T00:00:00Z","volume":32,"publisher":"Springer Nature","publication_status":"published","APC_amount":"12348 EUR","has_accepted_license":"1","OA_place":"publisher","language":[{"iso":"eng"}],"OA_type":"hybrid","external_id":{"oaworkid":["W4402316284"],"pmid":["39242978"],"isi":["001306564000001"]},"department":[{"_id":"FlSc"},{"_id":"LeSa"}],"pmid":1,"publication_identifier":{"issn":["1545-9993"],"eissn":["1545-9985"]},"citation":{"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.","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>","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>.","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.","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.","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>"},"article_processing_charge":"Yes (in subscription journal)","date_updated":"2026-03-16T12:55:18Z","_id":"17884"},{"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","file_date_updated":"2025-03-25T23:30:03Z","supervisor":[{"orcid":"0000-0003-4790-8078","first_name":"Florian KM","last_name":"Schur","full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"}],"alternative_title":["ISTA Thesis"],"publisher":"Institute of Science and Technology Austria","publication_status":"published","date_published":"2024-09-26T00:00:00Z","oa_version":"Published Version","ec_funded":1,"department":[{"_id":"GradSch"},{"_id":"FlSc"}],"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>","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.","ista":"Porley Esteves D. 2024. Structural characterization of spumavirus capsid assemblies. Institute of Science and Technology Austria.","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."},"publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-041-1"]},"has_accepted_license":"1","language":[{"iso":"eng"}],"OA_place":"publisher","_id":"18101","article_processing_charge":"No","date_updated":"2026-04-07T13:21:01Z","date_created":"2024-09-20T10:21:03Z","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."}],"type":"dissertation","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"file":[{"embargo_to":"open_access","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_created":"2024-09-26T13:40:33Z","file_name":"PhD_thesis_DPorley_final_20240919.docx","date_updated":"2025-03-25T23:30:03Z","creator":"dporley","access_level":"closed","relation":"source_file","file_id":"18149","file_size":14213128,"checksum":"3b8b0bacfe61112f3852744f3170e468"},{"embargo":"2025-03-25","date_created":"2024-09-26T13:41:39Z","content_type":"application/pdf","file_name":"PhD_thesis_DPorley_final_20240926_pdfa1.pdf","file_id":"18150","file_size":18583031,"checksum":"6c3a652a8eede874118e11d66a63652f","date_updated":"2025-03-25T23:30:03Z","access_level":"open_access","creator":"dporley","relation":"main_file"}],"oa":1,"corr_author":"1","status":"public","page":"131","day":"26","doi":"10.15479/at:ista:18101","year":"2024","project":[{"name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","call_identifier":"H2020"},{"name":"Structural characterization of spumavirus capsid assemblies to understand conserved Ortervirales assembly mechanisms","_id":"9B9C98E0-BA93-11EA-9121-9846C619BF3A","grant_number":"25762"}],"author":[{"id":"2FD6EA6C-F248-11E8-B48F-1D18A9856A87","full_name":"Porley, Dario J","first_name":"Dario J","last_name":"Porley"}],"degree_awarded":"PhD","ddc":["570"],"title":"Structural characterization of spumavirus capsid assemblies","month":"09"}]