National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01GM151775
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R21DE032878
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
F31AI184673
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
T32AI083196
米国
引用
ジャーナル: Nat Commun / 年: 2025 タイトル: High-resolution analysis of the human T-cell leukemia virus capsid protein reveals insights into immature particle morphology. 著者: William G Arndt / Alireza Ramezani / Nathaniel Talledge / Guichuan Yu / Huixin Yang / Bo Chen / Juan R Perilla / Wei Zhang / Louis M Mansky / 要旨: Infection with human T-cell leukemia virus type 1 (HTLV-1) can result in adult T-cell leukemia/lymphoma and HTLV-1 associated-myelopathy/tropical spastic paraparesis. The Gag polyprotein - the major ...Infection with human T-cell leukemia virus type 1 (HTLV-1) can result in adult T-cell leukemia/lymphoma and HTLV-1 associated-myelopathy/tropical spastic paraparesis. The Gag polyprotein - the major structural protein - is crucial for driving virus particle assembly, with the capsid (CA) domain as the key determinant for Gag multimerization. Here, we characterize the immature CA lattice from immature virus particles by using cryo-electron microscopy and tomography (cryo-EM/ET). We report resolving the immature CA lattice to 3.4 Å resolution by single particle analysis (SPA). Our reconstruction reveals that the lattice is stabilized through a trimeric NTD inter-hexamer interface and a dimeric CTD inter-hexamer interface. Further analysis by cryo-ET reveals clear heterogeneity, notably the varying lattice curvatures and the varying distances from the CA layer to the membrane. Intriguingly, inositol hexakisphosphate (IP6) is dispensable for HTLV-1 immature particle assembly and proper immature lattice formation. These observations provide deeper insights into the molecular basis of HTLV-1 immature particle morphology as well as aid in revealing therapeutic targets.
名称: Human T-cell leukemia virus type I / タイプ: virus / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: Virus particles were purified by co-transfecting in the HTLV-1 Gag and Env genes. NCBI-ID: 11908 / 生物種: Human T-cell leukemia virus type I / Sci species strain: B1033-2009 / ウイルスタイプ: VIRUS-LIKE PARTICLE / ウイルス・単離状態: STRAIN / ウイルス・エンベロープ: Yes / ウイルス・中空状態: No
トモグラム数: 9 / 使用した粒子像数: 41841 / ソフトウェア - 名称: Dynamo (ver. 1.1.532) 詳細: Surface of each virus particle was modeled as a sphere and coordinates were assigned evenly along the sphere surface.