Evidence map›Paper›PMID 40445428›Full record

ArticleActa neuropathologica2025

SARS-CoV-2 infection of human cortical cells is influenced by the interaction between aneuploidy and biological sex: insights from a Down syndrome in vitro model.

Maria I Lioudyno, Evgueni A Sevrioukov, Gema M Olivarria, Lauren Hitchcock, Dominic I Javonillo, Sydney M Campos, Isabel Rivera, Sierra T Wright, Elizabeth Head, Juan Fortea and 5 more

Abstract read
In one paragraph

Article in Acta neuropathologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

15 authors.

Maria I LioudynoDepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA. mlioudyn@uci.edu.
Evgueni A SevrioukovDepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA.
Gema M OlivarriaDepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA.
Lauren HitchcockDepartment of Medicine, Division of Infectious Diseases, UC Irvine School of Medicine, Irvine, CA, USA.
Dominic I JavonilloDepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA.
Sydney M CamposSamueli School of Engineering, University of California Irvine, Irvine, CA, USA.
Isabel RiveraDepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA.
Sierra T WrightDepartment of Pathology and Laboratory Medicine, Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA.
Elizabeth HeadDepartment of Pathology and Laboratory Medicine, Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA.
Juan ForteaSant Pau Memory Unit, Department of Neurology, Hospital de La Santa Creu I Sant Pau, Institut d'Investigació Biomèdica Sant Pau (IIB SANT PAU), Facultad de Medicina - Universitat Autònoma de Barcelona, Barcelona, Spain.
Thomas WisniewskiDepartments of Neurology, Pathology and Psychiatry and Center for Cognitive Neurology, New York University Grossman School of Medicine, New York, NY, USA.
A Claudio CuelloDepartment of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
Sonia Do CarmoDepartment of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
Thomas E LaneDepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA.
Jorge BusciglioDepartment of Neurobiology and Behavior, Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA. jbuscigl@uci.edu.

Funding

Research Education ComponentP30AG066512 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Mary Sherman Mittelman · 2020 to 2026
$28.4M
The Alzheimer's Disease Research Center at the University of California, IrvineP30AG066519 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Craig E Stark · 2020 to 2026
$27.9M
Transgenic/Behavior CoreP01AG060882 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI GONI, FERNANDO · 2020 to 2024
$12.0M
Training in the Neurobiology of Aging and Alzheimers DiseaseT32AG000096 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI VIVEK SWARUP, Craig E Stark · 1985 to 2026
$9.6M
Alzheimer’s Disease Related Biomarkers following SARS-CoV-2 InfectionR01AG077422 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Jennifer Ann Frontera, Yulin Ge · 2022 to 2026
$6.9M
DS-ARC: A Remote Digital Cognitive Assessment for Down Syndrome-Associated Alzheimer's DiseaseR01AG081394 · NIA · WASHINGTON UNIVERSITY · PI Jason J Hassenstab · 2023 to 2026
$6.0M
The Role of Inflammation and NGF Dysfunction in the Evolution of Alzheimer Disease Pathology in Down Syndrome-RevisionRF1AG056850 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BUSCIGLIO, JORGE A, CUELLO, A CLAUDIO · 2018 to 2020
$5.9M
Clinical trials to prevent Alzheimer's Disease in Down SyndromeR61AG066543 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI RAFII, MICHAEL S · 2019 to 2020
$5.6M
Tau pathology in Down syndrome and Alzheimer'sRF1AG061566 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI GRANHOLM-BENTLEY, ANN-CHARLOTTE ESTHER, MARGITTAI, MARTIN · 2019 to 2019
$3.4M
The role of immune deregulation and NGF dysmetabolism in the development of Alzheimer disease in individuals with Down syndromeR01AG087280 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI JORGE A BUSCIGLIO, A CLAUDIO CUELLO · 2024 to 2026
$3.2M
Virus-host interactions: a multi-scale training programT32AI007319 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI SEMLER, BERT L, SHI, YONGSHENG · 1988 to 2024
$2.4M
Training in Translational ADRD Neuroscience (TITAN)T32AG073088 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Joshua Grill, Elizabeth Head · 2021 to 2026
$2.2M
ALZ Discovery grant from the Alzheimer's Association 1051950Centro de Investigación Biomédica en Red sobre Enfermedades IIBSP-DOW-2020-151Horizon 2020-Research and Innovation Framework Programme from the European Union H2020-SC1-BHC-2018-2020Instituto de Salud Carlos III (Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España) INT21/00073NIAID NIH HHS T32 AI007319NIA NIH HHS P01 AG060882NIA NIH HHS P30 AG066512NIA NIH HHS P30 AG066519NIA NIH HHS R01 AG077422NIA NIH HHS R01 AG081394NIA NIH HHS R01 AG087280NIA NIH HHS R21 AG056974NIA NIH HHS R61 AG066543NIA NIH HHS RF1 AG056850NIA NIH HHS RF1 AG061566NIA NIH HHS T32 AG000096NIA NIH HHS T32 AG073088NIH HHS T32 AG000096NINDS NIH HHS T32 NS121727US National Institutes of Health 5T32 AI007319-33US National Institutes of Health P30AG066519US National Institutes of Health RO1AG056850US National Institutes of Health T32 T32NS121727
6 · The paper itself

Abstract

Individuals with Down Syndrome (DS) represent one of the most susceptible populations for developing severe COVID-19, and a unique human genetic condition for investigating molecular mechanisms underlying susceptibility of neurologically vulnerable individuals to SARS-CoV-2 infection. Human Chromosome-21 (HSA21) triplication in DS causes global transcriptional deregulation, affecting multiple genes that may directly (e.g., TMPRSS2) or indirectly influence the SARS-CoV-2 entry into central nervous system (CNS) cells. The anti-viral immune response may also be altered in cells with trisomy-21 (T21) due to triplication of genes encoding for several interferon receptor subunits and interferon-stimulated genes (ISGs). Here, we demonstrate that human cells derived from fetal cortical specimens and maintained in primary cultures are susceptible to infection with a molecular clone of vesicular stomatitis virus engineered to express the Spike protein of SARS-CoV-2 (VSV-eGFP-SARS-CoV-2) and to authentic SARS-CoV-2. The level of SARS-CoV-2 infectivity in cultures originated from different cortical specimens varied, seemingly depending on ploidy and chromosomal sex of the cells. We confirmed the presence of ACE2 and TMPRSS2 in cultures and found that XY T21 group had the highest TMPRSS2 mRNA levels, which was associated with increased infectivity in XY-compared to XX T21 cultures. The XX T21 cultures exhibited elevated expression of several ISGs (MX1, STAT1, and STAT2) which was associated with lower infectivity. The comparisons of postmortem aged brain specimens revealed reduced ACE2, TMPRSS2, but elevated STAT2 protein levels in individuals with DS and Alzheimer's disease (DS-AD) compared to control and Alzheimer's disease (AD) group. Collectively, these results suggest multifactorial regulation of SARS-CoV-2 infectivity in cortical cells that involves ploidy, chromosomal sex, and the expression of genes implicated in regulation of virus entry and anti-viral response as contributing factors.

Indexed as

AneuploidyCerebral CortexCOVID-19Down SyndromeSARS-CoV-2Cells, CulturedFemaleHumansMaleSerine EndopeptidasesSerine EndopeptidasesTMPRSS2 protein, humanInterferon systemPostmortem brain specimensPrimary cortical culturesSARS-CoV-2Sex differencesTrisomy-21

Identifiers

PMID40445428
PMCPMC12125050

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.