Obr Martin, Percipalle Mathias, Chernikova Darya, Yang Huixin, Thader Andreas, Pinke Gergely, Porley Dario, Mansky Louis M, Dick Robert A, Schur Florian K M
Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria.
Material and Structural Analysis Division, Thermo Fisher Scientific, Achtseweg Noord, Eindhoven, Netherlands.
Nat Struct Mol Biol. 2025 Feb;32(2):268-276. doi: 10.1038/s41594-024-01390-8. Epub 2024 Sep 6.
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.
人类嗜T淋巴细胞病毒1型(HTLV-1)未成熟颗粒在形态上与其他逆转录病毒不同,这表明其组装方式独特。在此,我们报告了对体外组装以及来源于细胞的HTLV-1病毒样颗粒进行冷冻电子断层扫描研究的结果。这项工作表明,HTLV-1利用一种独特的Gag-Gag相互作用机制来形成未成熟病毒晶格。对未成熟衣壳(CA)管状阵列的高分辨率结构信息分析表明,HTLV-1中的主要稳定成分是CA的N端结构域。诱变分析支持了这一观察结果。这使HTLV-1与其他逆转录病毒区分开来,在其他逆转录病毒中,稳定作用主要由CA的C端结构域提供。这些结果提供了未成熟δ逆转录病毒Gag四级排列的结构细节,这有助于解释为什么HTLV-1颗粒在形态上与众不同。