人1型嗜T细胞白血病病毒未成熟Gag晶格的非常规稳定化

Unconventional stabilization of the human T-cell leukemia virus type 1 immature Gag lattice.

作者信息

Obr Martin, Percipalle Mathias, Chernikova Darya, Yang Huixin, Thader Andreas, Pinke Gergely, Porley Dario, Mansky Louis M, Dick Robert A, Schur Florian Km

机构信息

Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria.

Institute for Molecular Virology, University of Minnesota, Minneapolis, MN, USA.

出版信息

bioRxiv. 2023 Jul 24:2023.07.24.548988. doi: 10.1101/2023.07.24.548988.

DOI:10.1101/2023.07.24.548988

PMID:37546793

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10402013/

Abstract

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 , 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.

摘要

与其他逆转录病毒相比，人类1型T细胞白血病病毒（HTLV-1）具有非典型的未成熟颗粒形态。这表明这些颗粒以独特的方式形成。在此，我们报告了对组装的以及源自细胞的HTLV-1病毒样颗粒（VLP）进行冷冻电子断层扫描（cryo-ET）研究的结果。这项工作表明，HTLV-1采用非常规的Gag-Gag相互作用机制来形成未成熟的病毒晶格。对未成熟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-NTD。诱变和生物物理分析支持这一观察结果。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，稳定主要由CA-CTD提供。这些结果首次提供了未成熟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。