Evidence map›Paper›PMID 35215199›Full record

ArticlePathogens (Basel, Switzerland)2022

SARS-CoV-2 Infects Primary Neurons from Human ACE2 Expressing Mice and Upregulates Genes Involved in the Inflammatory and Necroptotic Pathways.

Hussin A Rothan, Pratima Kumari, Shannon Stone, Janhavi P Natekar, Komal Arora, Tabassum T Auroni, Mukesh Kumar

Open access · goldAbstract read
In one paragraph

Article in Pathogens (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 6% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. SARS-CoV-2 XBB.1.5 infects wild-type C57BL/6 mice and induces a protective CD4Frontiers in cellular and infection microbiology · 2025
    Article
  8. Article
  9. Article
  10. A suitable model to investigate acute neurological consequences of coronavirus infection.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023
    Article
  11. The role of cell death in SARS-CoV-2 infection.Signal transduction and targeted therapy · 2023
    Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. ZBP1 and heatstroke.Frontiers in immunology · 2023
    Review
  17. Article
  18. Review
  19. Neuro-Immune Interactions in Severe COVID-19 Infection.Pathogens (Basel, Switzerland) · 2022
    Review
  20. Review
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

7 authors at 1 institution in 1 country.

Hussin A RothanDepartment of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.ORCID 0000-0002-7300-6388
Pratima KumariDepartment of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
Shannon StoneDepartment of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
Janhavi P NatekarDepartment of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
Komal AroraDepartment of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.
Tabassum T AuroniDepartment of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.ORCID 0000-0002-5929-2728
Mukesh KumarDepartment of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA.ORCID 0000-0003-0970-4875
Georgia State University · US

Funding

A Guinea Pig Model of Zika Virus DiseaseR21OD024896 · OD · UNIVERSITY OF HAWAII AT MANOA · PI KUMAR, MUKESH · 2017 to 2018
$402k
NIH HHS R21 OD024896
6 · The paper itself

Abstract

Transgenic mice expressing human angiotensin-converting enzyme 2 under the cytokeratin 18 promoter (K18-hACE2) have been extensively used to investigate the pathogenesis and tissue tropism of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Neuroinvasion and the replication of SARS-CoV-2 within the central nervous system (CNS) of K18-hACE2 mice is associated with increased mortality; although, the mechanisms by which this occurs remain unclear. In this study, we generated primary neuronal cultures from K18-hACE2 mice to investigate the effects of a SARS-CoV-2 infection. We also evaluated the immunological response to SARS-CoV-2 infection in the CNS of K18-hACE2 mice and mouse neuronal cultures. Our data show that neuronal cultures obtained from K18-hACE2 mice are permissive to SARS-CoV-2 infection and support productive virus replication. Furthermore, SARS-CoV-2 infection upregulated the expression of genes involved in innate immunity and inflammation, including IFN-α, ISG-15, CXCL10, CCL2, IL-6 and TNF-α, in the neurons and mouse brains. In addition, we found that SARS-CoV-2 infection of neurons and mouse brains activates the ZBP1/pMLKL-regulated necroptosis pathway. Together, our data provide insights into the neuropathogenesis of SARS-CoV-2 infection in K18-hACE2 mice.

Indexed as

COVID-19inflammationK18-hACE2 micenecroptosisneuronsneuropathogenesisSARS-CoV-2

Identifiers

PMID35215199
PMCPMC8876293
OpenAlexW4212846497

What OpenQuestion 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 OpenQuestion graph.