Evidence map›Paper›PMID 40987287›Full record

ArticleCell reports2025

Old World alphaviruses use distinct mechanisms to infect brain microvascular endothelial cells for neuroinvasion.

Pablo A Alvarez, Ashley Tang, Declan M Winters, Prashant Kaushal, Angelica Medina, Maria Villalba Nieto, Karolina E Kaczor-Urbanowicz, Faith St Amant, Bryan Ramirez Reyes, Robyn M Kaake and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. International journal of molecular sciences · 2026
    Article
  7. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Pablo A AlvarezDepartment of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Ashley TangDepartment of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Declan M WintersDepartment of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Prashant KaushalDepartment of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Angelica MedinaDepartment of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
Maria Villalba NietoDepartment of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Karolina E Kaczor-UrbanowiczInstitute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA; Center of Oral and Head/Neck Oncology Research, Biosystems and Function, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Faith St AmantDepartment of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Bryan Ramirez ReyesMolecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Robyn M KaakeDepartment of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, Gladstone Institute for Data Science and Biotechnology, San Francisco, CA 94158, USA.
Oliver I FregosoDepartment of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
April D PyleDepartment of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Mehdi BouhaddouDepartment of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Hengli TangDepartment of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
Melody M H LiDepartment of Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: manhingli@mednet.ucla.edu.

Funding

MULTIDISCIPLINARY TRAINING IN MICROBIAL PATHOGENESIST32AI007323 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Peter John Bradley · 1988 to 2026
$8.6M
Reprogramming and Directed Differentiation of Skeletal Muscle Cells from hPSCs.R01AR064327 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI April D Pyle · 2013 to 2026
$6.4M
Research Training in Cell and Molecular BiologyT32GM145388 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Jorge Torres · 2022 to 2026
$5.2M
Unraveling alphavirus neuroinvasion: Molecular insights from a stem cell based blood-brain barrier modelF31AI179235 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ALVAREZ, PABLO · 2024 to 2025
$68k
NIAID NIH HHS F31 AI179235NIAID NIH HHS T32 AI007323NIAMS NIH HHS R01 AR064327NIGMS NIH HHS T32 GM145388
6 · The paper itself

Abstract

Several alphaviruses bypass the blood-brain barrier (BBB), causing debilitating or fatal encephalitis. Sindbis virus (SINV) has been extensively studied in vivo to understand alphavirus neuropathogenesis, yet the molecular details of neuroinvasion remain poorly understood. We investigated alphavirus-BBB interactions by pairing a physiologically relevant, human pluripotent stem cell-derived model of brain microvascular endothelial-like cells with SINV strains of opposite neuroinvasiveness. Our system demonstrates that SINV neuroinvasion correlates with robust BBB infection. Specifically, SINV genetic determinants of neuroinvasion enhance viral entry into human pluripotent stem cell-derived brain microvascular endothelial-like cells. We also demonstrate that neuroinvasive SINV relies primarily on PCDH10, while non-neuroinvasive SINV relies on multiple entry factors, including LRP1. This specialist-versus-generalist strategy is what ultimately modulates neuroinvasion. Strikingly, efficient BBB infection is a conserved phenotype that correlates with the neuroinvasive capacity of several Old World alphaviruses, including chikungunya virus. We reveal BBB infection as a shared pathway for alphavirus neuroinvasion that can be targeted to prevent alphavirus-induced encephalitis.

Indexed as

AlphavirusAlphavirus InfectionsBlood-Brain BarrierBrainEndothelial CellsMicrovesselsSindbis VirusAnimalsCadherinsHumansVirus InternalizationCadherinsalphavirusblood-brain barrierbrain microvascular endothelial cellsCP: Microbiologyhuman pluripotent stem cell-derived modelneuroinvasionvirus entryvirus receptor

Identifiers

PMID40987287
PMCPMC12617940

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.