article published yes Martin Obr author 4741CA5A-F248-11E8-B48F-1D18A9856A870000-0003-1756-6564 Mathias Percipalle author 4986e21c-eb97-11eb-a6c2-a4ef0b629971 Darya Chernikova author 7dbaf460-fa9e-11eb-b0ca-bc7c7ff21ad0 Huixin Yang author Andreas Thader author 3A18A7B8-F248-11E8-B48F-1D18A9856A87 Gergely Pinke author 4D5303E6-F248-11E8-B48F-1D18A9856A87 Dario J Porley author 2FD6EA6C-F248-11E8-B48F-1D18A9856A87 Louis M. Mansky author Robert A. Dick author Florian KM Schur author 48AD8942-F248-11E8-B48F-1D18A9856A870000-0003-4790-8078 FlSc department LeSa department Structural conservation and diversity in retroviral capsid project Structural characterization of spumavirus capsid assemblies to understand conserved Ortervirales assembly mechanisms project 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. https://research-explorer.ista.ac.at/download/17884/19608/2025_NatureStrucBio_Obr.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Springer Nature2025 eng 1545-9993 1545-9985 39242978 00130656400000110.1038/s41594-024-01390-8 32268-276 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. 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> 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> 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. 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. 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>. 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>. 178842024-09-08T10:29:06Z2026-03-16T12:55:18Z