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TitleHigh-resolution analysis of the human T-cell leukemia virus capsid protein reveals insights into immature particle morphology.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Page 444, Year 2025
Publish dateDec 11, 2025
AuthorsWilliam G Arndt / Alireza Ramezani / Nathaniel Talledge / Guichuan Yu / Huixin Yang / Bo Chen / Juan R Perilla / Wei Zhang / Louis M Mansky /
PubMed AbstractInfection 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.
External linksNat Commun / PubMed:41381513 / PubMed Central
MethodsEM (subtomogram averaging) / EM (single particle)
Resolution3.44 - 7.82 Å
Structure data

EMDB-48795: Subtomogram averaging of HTLV-1 Gag capsid from immature particles
Method: EM (subtomogram averaging) / Resolution: 7.82 Å

48796

9n0w

9n92

EMDB-48796, PDB-9n0w:
HTLV-1 Gag capsid from immature particles
PDB-9n92: High-resolution analysis of the human T-cell leukemia virus capsid protein reveals insights into immature particle morphology
Method: EM (single particle) / Resolution: 3.44 Å

Chemicals

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE

Source
  • human t-cell leukemia virus type i
KeywordsVIRAL PROTEIN / Complex / virus / lattice / VIRUS LIKE PARTICLE / capsid / gag / HTLV

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