Distinct stabilization of the human T cell leukemia virus type 1 immature Gag lattice
Obr M, Percipalle M, Chernikova D, Yang H, Thader A, Pinke G, Porley DJ, Mansky LM, Dick RA, Schur FK. 2024. Distinct stabilization of the human T cell leukemia virus type 1 immature Gag lattice. Nature Structural & Molecular Biology.
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Obr, MartinISTA 
;
Percipalle, MathiasISTA;
Chernikova, DaryaISTA;
Yang, Huixin;
Thader, AndreasISTA;
Pinke, GergelyISTA;
Porley, Dario JISTA;
Mansky, Louis M.;
Dick, Robert A.;
Schur, FlorianISTA
;
Percipalle, MathiasISTA;
Chernikova, DaryaISTA;
Yang, Huixin;
Thader, AndreasISTA;
Pinke, GergelyISTA;
Porley, Dario JISTA;
Mansky, Louis M.;
Dick, Robert A.;
Schur, FlorianISTA Department
Grant
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.
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Date Published
2024-09-06
Journal Title
Nature Structural & Molecular Biology
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.
Acknowledged SSUs
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IST-REx-ID
Cite this
Obr M, Percipalle M, Chernikova D, et al. Distinct stabilization of the human T cell leukemia virus type 1 immature Gag lattice. Nature Structural & Molecular Biology. 2024. doi:10.1038/s41594-024-01390-8
Obr, M., Percipalle, M., Chernikova, D., Yang, H., Thader, A., Pinke, G., … Schur, F. K. (2024). Distinct stabilization of the human T cell leukemia virus type 1 immature Gag lattice. Nature Structural & Molecular Biology. Springer Nature. https://doi.org/10.1038/s41594-024-01390-8
Obr, Martin, Mathias Percipalle, Darya Chernikova, Huixin Yang, Andreas Thader, Gergely Pinke, Dario J Porley, Louis M. Mansky, Robert A. Dick, and Florian KM Schur. “Distinct Stabilization of the Human T Cell Leukemia Virus Type 1 Immature Gag Lattice.” Nature Structural & Molecular Biology. Springer Nature, 2024. https://doi.org/10.1038/s41594-024-01390-8.
M. Obr et al., “Distinct stabilization of the human T cell leukemia virus type 1 immature Gag lattice,” Nature Structural & Molecular Biology. Springer Nature, 2024.
Obr M, Percipalle M, Chernikova D, Yang H, Thader A, Pinke G, Porley DJ, Mansky LM, Dick RA, Schur FK. 2024. Distinct stabilization of the human T cell leukemia virus type 1 immature Gag lattice. Nature Structural & Molecular Biology.
Obr, Martin, et al. “Distinct Stabilization of the Human T Cell Leukemia Virus Type 1 Immature Gag Lattice.” Nature Structural & Molecular Biology, Springer Nature, 2024, doi:10.1038/s41594-024-01390-8.
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