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TitleStructural insights into the dynamic mechanism of bornavirus polymerase.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 122, Issue 39, Page e2504779122, Year 2025
Publish dateSep 30, 2025
AuthorsGe Yang / Dong Wang / Bin Liu /
PubMed AbstractBorna disease virus 1 (BoDV-1), an emerging zoonotic pathogen from the family, is neurotropic and can infect a variety of mammalian hosts, including humans. Linked to severe encephalitis and high ...Borna disease virus 1 (BoDV-1), an emerging zoonotic pathogen from the family, is neurotropic and can infect a variety of mammalian hosts, including humans. Linked to severe encephalitis and high mortality, BoDV-1 currently lacks licensed treatments or vaccines. The BoDV-1 polymerase complex, comprising the large (L) and phosphoprotein (P) subunits, is crucial for viral replication and transcription, making it a promising target for antiviral intervention. Here, we present the cryoelectron microscopy structure of the apo BoDV-1 L-P complex, revealing a unique "mitten-shaped" architecture. The structure characterizes key domains involved in RNA synthesis, including RNA-dependent RNA polymerase, polyribonucleotidyltransferase, and an inactive methyltransferase domain. While no RNA or NTPs were visible, we observed distinct conformational states, showing large-scale rearrangements of the P tetramer and L domains, as well as remodeling of the RNA template, nucleoside triphosphates, and nascent RNA entrances and/or exits, upon introducing RNA and NTPs. These findings highlight the dynamic structural changes probably associated with polymerase activity and advance the understanding of the BoDV-1 polymerase mechanisms, offering a basis for developing targeted antiviral strategies against this deadly pathogen.
External linksProc Natl Acad Sci U S A / PubMed:40996804 / PubMed Central
MethodsEM (single particle)
Resolution2.71 - 3.47 Å
Structure data

EMDB-48790, PDB-9n0q:
3.09A Bornavirus L-P complex (without incubation with RNA/NTP) (state 1)
Method: EM (single particle) / Resolution: 3.09 Å

EMDB-48791, PDB-9n0r:
2.71A Bornavirus L-P complex (after incubation with RNA/NTP) (state 1)
Method: EM (single particle) / Resolution: 2.71 Å

EMDB-48792, PDB-9n0s:
3.47A Bornavirus L-P complex (after incubation with RNA/NTP) (state 2)
Method: EM (single particle) / Resolution: 3.47 Å

EMDB-48793, PDB-9n0t:
3.37A Bornavirus L-P complex (after incubation with RNA/NTP) (state 3)
Method: EM (single particle) / Resolution: 3.37 Å

EMDB-48794, PDB-9n0u:
3.46A Bornavirus L-P complex (after incubation with RNA/NTP) (state 4)
Method: EM (single particle) / Resolution: 3.46 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • orthobornavirus
KeywordsTRANSFERASE / VIRAL PROTEIN / Bornavirus / L protein / phosphoprotein / RNA-dependent RNA polymerase / PRNTase / GDP polyribonucleotidyl transferase / RNA capping / viral replication

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