Unconventional stabilization of the human T-cell leukemia virus type 1 immature Gag lattice.
Unconventional stabilization of the human T-cell leukemia virus type 1 immature Gag lattice.
复制标题
人类 T 细胞白血病病毒 1 型未成熟 Gag 晶格的非常规稳定。
DOI：
10.1101/2023.07.24.548988
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Schur,FlorianKm
中科院分区：
文献类型：
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作者：
Obr,Martin;Percipalle,Mathias;Chernikova,Darya;Yang,Huixin;Thader,Andreas;Pinke,Gergely;Porley,Dario;Mansky,LouisM;Dick,RobertA;Schur,FlorianKm
人类t细胞白血病病毒1型（HTLV-1）与其他逆转录病毒相比具有非典型的未成熟颗粒形态。这表明这些粒子以一种独特的方式形成。在这里，我们报告了HTLV-1病毒样颗粒（vlp）体外组装和细胞衍生的低温电子断层扫描（cryo-ET）研究的结果。这项工作表明HTLV-1采用一种非常规的Gag-Gag相互作用机制来形成未成熟的病毒晶格。来自未成熟CA管状阵列的高分辨率结构信息分析表明，HTLV-1的主要稳定成分是CA- ntd。诱变和生物物理分析支持这一观察。这将HTLV-1与其他逆转录病毒区别开来，在其他逆转录病毒中，稳定化主要由CA-CTD提供。这些结果首次提供了未成熟三角逆转录病毒Gag的四级排列结构细节，这有助于解释HTLV-1颗粒在形态上不同的原因。
Human T-cell leukemia virus type 1 (HTLV-1) has an atypical immature particle morphology compared to other retroviruses. This indicates that these particles are formed in a way that is unique. Here we report the results of cryo-electron tomography (cryo-ET) studies of HTLV-1 virus-like particles (VLPs) assembled in vitro, as well as derived from cells. This work shows that HTLV-1 employs an unconventional mechanism of Gag-Gag interactions to form the immature viral lattice. Analysis of high-resolution structural information from immature CA tubular arrays reveals that the primary stabilizing component in HTLV-1 is CA-NTD. Mutagenesis and biophysical analysis support this observation. This distinguishes HTLV-1 from other retroviruses, in which the stabilization is provided primarily by the CA-CTD. These results are the first to provide structural details of the quaternary arrangement of Gag for an immature deltaretrovirus, and this helps explain why HTLV-1 particles are morphologically distinct.