Evidence map›Paper›PMID 40187345›Full record

ArticleCell2025

Molecular basis for shifted receptor recognition by an encephalitic arbovirus.

Xiaoyi Fan, Wanyu Li, Jessica Oros, Jessica A Plante, Brooke M Mitchell, Jesse S Plung, Himanish Basu, Sivapratha Nagappan-Chettiar, Joshua M Boeckers, Laurentia V Tjang and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

11 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Xiaoyi FanDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Wanyu LiDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Jessica OrosDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Jessica A PlanteWorld Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
Brooke M MitchellWorld Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
Jesse S PlungDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Himanish BasuDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Sivapratha Nagappan-ChettiarDepartment of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Joshua M BoeckersDepartment of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Laurentia V TjangDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Colin J MannDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Vesna BrusicDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Tierra K BuckDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Haley VarnumDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Pan YangDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Linzy M MalcolmDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
So Yoen ChoiDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
William M de SouzaDepartment of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY, USA.
Isaac M ChiuDepartment of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Hisashi UmemoriDepartment of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Scott C WeaverWorld Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
Kenneth S PlanteWorld Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA; Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
Jonathan AbrahamDepartment of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA; Department of Medicine, Division of Infectious Diseases, Brigham & Women's Hospital, Boston, MA, USA; Center for Integrated Solutions for Infectious Diseases, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA. Electronic address: jonathan_abraham@hms.harvard.edu.

Funding

Training in the Molecular Biology of Neurodegeneration and Alzheimer's DiseaseT32AG000222 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Bruce A YANKNER · 1992 to 2026
$18.5M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
MOLECULAR BASIS OF VIRAL INFECTIVITYT32AI007245 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Aaron Gregory Schmidt · 1985 to 2026
$11.3M
World Reference Center for Emerging Viruses and Arboviruses (WRCEVA)R24AI120942 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI WEAVER, SCOTT C · 2016 to 2024
$8.5M
Molecular Codes for the Establishment of Functionally Segregated Dopaminergic CircuitsR01MH125162 · NIMH · BOSTON CHILDREN'S HOSPITAL · PI UMEMORI, HISASHI, WATABE-UCHIDA, MITSUKO · 2021 to 2025
$4.1M
Structural and functional studies of alphavirus receptorsR01AI182377 · NIAID · HARVARD MEDICAL SCHOOL · PI Jonathan Abraham · 2024 to 2026
$2.2M
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI182377NIAID NIH HHS R24 AI120942NIAID NIH HHS T32 AI007245NIA NIH HHS T32 AG000222NIGMS NIH HHS T32 GM008313NIGMS NIH HHS T32 GM144273NIMH NIH HHS R01 MH125162Wellcome Trust
6 · The paper itself

Abstract

Western equine encephalitis virus (WEEV) is an arbovirus that historically caused large outbreaks of encephalitis throughout the Americas. WEEV binds protocadherin 10 (PCDH10) as a receptor, and highly virulent ancestral WEEV strains also bind low-density lipoprotein receptor (LDLR)-related proteins. As WEEV declined as a human pathogen in North America over the past century, isolates have lost the ability to bind mammalian receptors while still recognizing avian receptors. To explain shifts in receptor dependencies and assess the risk of WEEV re-emergence, we determined cryoelectron microscopy structures of WEEV bound to human PCDH10, avian PCDH10, and human very-low-density lipoprotein receptor (VLDLR). We show that one to three E2 glycoprotein substitutions are sufficient for a nonpathogenic strain to regain the ability to bind mammalian receptors. A soluble VLDLR fragment protects mice from lethal challenge by a virulent ancestral WEEV strain. Because WEEV recently re-emerged in South America after decades of inactivity, our findings have important implications for outbreak preparedness.

Indexed as

CadherinsReceptors, LDLAnimalsArbovirusesCryoelectron MicroscopyFemaleHumansMiceProtein BindingViral Envelope ProteinsCadherinsReceptors, LDLViral Envelope ProteinsVLDL receptoralphavirusarbovirusemerging virusencephalitisreceptorviral glycoprotein

Identifiers

PMID40187345
PMCPMC12406711

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.