Evidence map›Paper›PMID 38525304›Full record

ArticlePNAS nexus2024

Cryogenic electron microscopy and tomography reveal imperfect icosahedral symmetry in alphaviruses.

David Chmielewski, Guan-Chin Su, Jason T Kaelber, Grigore D Pintilie, Muyuan Chen, Jing Jin, Albert J Auguste, Wah Chiu

Open access · goldAbstract read
In one paragraph

Article in PNAS nexus, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Cryo-EM structure of the Rift Valley fever virus envelope protein in complex with a potent neutralization antibody.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 1 country.

David ChmielewskiBiophysics Graduate Program, Stanford University, Stanford, CA 94305, USA.ORCID https://orcid.org/0000-0002-4498-7949
Guan-Chin SuDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.ORCID https://orcid.org/0000-0003-3251-5511
Jason T KaelberInstitute for Quantitative Biomedicine, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.ORCID https://orcid.org/0000-0001-9426-1030
Grigore D PintilieDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA.ORCID https://orcid.org/0000-0002-0848-5335
Muyuan ChenDivision of CryoEM and Bioimaging, SSRL, SLAC National Accelerator Laboratory, Stanford University, Menlo Park, CA 94025, USA.
Jing JinVitalant Research Institute, San Francisco, CA 94118, USA.
Albert J AugusteDepartment of Entomology, College of Agriculture and Life Sciences, Fralin Life Science Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.ORCID https://orcid.org/0000-0001-9048-0041
Wah ChiuBiophysics Graduate Program, Stanford University, Stanford, CA 94305, USA.ORCID https://orcid.org/0000-0002-8910-3078
Stanford University · USSLAC National Accelerator Laboratory · USRutgers, The State University of New Jersey · USUniversity of California, San Francisco · USVirginia Tech · US

Funding

3 D ELECTRON MICROSCOPY OF MACROMOLECULES (5P41RR002250-27)P41GM103832 · NIGMS · STANFORD UNIVERSITY · PI CHIU, WAH · 2012 to 2019
$15.1M
Acquisition of a 300 kV Electron Microscope for Structural BiologyS10OD021600 · OD · STANFORD UNIVERSITY · PI CHIU, WAH · 2016 to 2016
$2.0M
A Novel Strategy for Generating Safe and Effective Flavivirus VaccinesR01AI153433 · NIAID · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI AUGUSTE, ALBERT J. · 2020 to 2024
$2.0M
NIAID NIH HHS R01 AI153433NIGMS NIH HHS P41 GM103832NIH HHS S10 OD021600
6 · The paper itself

Abstract

Alphaviruses are spherical, enveloped RNA viruses with two-layered icosahedral architecture. The structures of many alphaviruses have been studied using cryogenic electron microscopy (cryo-EM) reconstructions, which impose icosahedral symmetry on the viral particles. Using cryogenic electron tomography (cryo-ET), we revealed a polarized symmetry defect in the icosahedral lattice of Chikungunya virus (CHIKV) in situ, similar to the late budding particles, suggesting the inherent imperfect symmetry originates from the final pinch-off of assembled virions. We further demonstrated this imperfect symmetry is also present in in vitro purified CHIKV and Mayaro virus, another arthritogenic alphavirus. We employed a subparticle-based single-particle analysis protocol to circumvent the icosahedral imperfection and boosted the resolution of the structure of the CHIKV to ∼3 Å resolution, which revealed detailed molecular interactions between glycoprotein E1-E2 heterodimers in the transmembrane region and multiple lipid-like pocket factors located in a highly conserved hydrophobic pocket. This complementary use of in situ cryo-ET and single-particle cryo-EM approaches provides a more precise structural description of near-icosahedral viruses and valuable insights to guide the development of structure-based antiviral therapies against alphaviruses.

Indexed as

alphaviruscryo-EMcryo-ETimperfect icosahedral symmetry

Identifiers

PMID38525304
PMCPMC10959069
OpenAlexW4392544853

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.