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TitleIntegrase anchors viral RNA to the HIV-1 capsid interior.
Journal, issue, pagesNature, Year 2026
Publish dateFeb 18, 2026
AuthorsMatthew R Singer / Zhen Li / Juan S Rey / Joshua Hope / Florian Chenavier / Nicola J Cook / Emma Punch / Jamie Smith / Zhiyu Zhou / Sarah Maslen / Laura Masino / Andrea Nans / Mark Skehel / Ian A Taylor / Giulia Zanetti / Peijun Zhang / Juan R Perilla / Alan N Engelman / Peter Cherepanov /
PubMed AbstractHIV-1 integrase (IN) promotes encapsulation of viral genomic RNA into mature viral cores, and this function is a target for ongoing antiretroviral drug development efforts. Here we determined the ...HIV-1 integrase (IN) promotes encapsulation of viral genomic RNA into mature viral cores, and this function is a target for ongoing antiretroviral drug development efforts. Here we determined the cryogenic electron microscopy (cryo-EM) structure of a primate lentiviral IN in a complex with RNA, revealing a linear filament made of IN octamer repeat units, each comprising a pair of asymmetric homotetramers. The assembly is stabilized through IN-RNA interactions involving mainly the IN C-terminal domains and RNA backbone. The spacing and orientation of the IN filament repeat units closely matched those of consecutive capsid (CA) hexamers within the mature CA lattice. Using cryo-EM images of native purified HIV-1 cores, we refined the structure of the IN filament as it propagates along the luminal side of the CA lattice. Each IN tetramer within the filament nestled in a CA hexamer, engaging closely with the major homology regions. Substitutions of residues involved in IN-CA contacts yielded eccentric virions with RNA nucleoids located outside of the cores. Collectively, our results establish the structural basis for the HIV-1 IN-RNA interaction and reveal that IN forms an RNA-binding module on the luminal side of the mature CA lattice.
External linksNature / PubMed:41708858
MethodsEM (single particle)
Resolution3.3 - 4.63 Å
Structure data

54068

9rmu

EMDB-54068, PDB-9rmu:
SIVtal integrase in complex with RNA stem-loop (focused refinement of the filament repeat unit)
Method: EM (single particle) / Resolution: 3.3 Å

54071

9rmx

EMDB-54071, PDB-9rmx:
CryoEM reconstruction of integrase filament at the lumen of native HIV-1 cores (box size 34.2 nm)
Method: EM (single particle) / Resolution: 4.63 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-IHP:
INOSITOL HEXAKISPHOSPHATE

Source
  • simian immunodeficiency virus
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN / Integrase / RNA / Octamer / SIVtal / capsid / HIV-1

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