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bioRxiv · 10.1101/2023.07.24.548988

Unconventional 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, D.·Mansky, L. M.·Dick, R.·Schur, F. K.
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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 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.

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Obr, M., Percipalle, M., Chernikova, D., Yang, H., Thader, A., Pinke, G., Porley, D., Mansky, L. M., Dick, R., Schur, F. K.. 2023-07-24. Unconventional stabilization of the human T-cell leukemia virus type 1 immature Gag lattice. https://doi.org/10.1101/2023.07.24.548988

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