Evidence map›Paper›PMID 33838105›Full record

ArticleCell stem cell2021

Organoid modeling of Zika and herpes simplex virus 1 infections reveals virus-specific responses leading to microcephaly.

Veronica Krenn, Camilla Bosone, Thomas R Burkard, Julia Spanier, Ulrich Kalinke, Arianna Calistri, Cristiano Salata, Raissa Rilo Christoff, Patricia Pestana Garcez, Ali Mirazimi and 1 more

Open access · greenAbstract read
In one paragraph

Article in Cell stem cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
9.0field-weighted citation impact, top 1% 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

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.

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  20. Organoids: physiologically relevantJournal of virology · 2025
    Review

28 more citing papers are in PubMed but not listed here.

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

11 authors at 7 institutions in 5 countries.

Veronica KrennInstitute of Molecular Biotechnology (IMBA), Austrian Academy of Sciences, Vienna BioCenter (VBC), Vienna 1030, Austria.
Camilla BosoneInstitute of Molecular Biotechnology (IMBA), Austrian Academy of Sciences, Vienna BioCenter (VBC), Vienna 1030, Austria.
Thomas R BurkardInstitute of Molecular Biotechnology (IMBA), Austrian Academy of Sciences, Vienna BioCenter (VBC), Vienna 1030, Austria.
Julia SpanierInstitute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research, Braunschweig, and the Hanover Medical School, Hanover 30625, Germany.
Ulrich KalinkeInstitute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Helmholtz Centre for Infection Research, Braunschweig, and the Hanover Medical School, Hanover 30625, Germany; Cluster of Excellence - Resolving Infection Susceptibility (RESIST), Hanover Medical School, Hanover 30625, Germany.
Arianna CalistriDepartment of Molecular Medicine, University of Padua, Padua 35121, Italy.
Cristiano SalataDepartment of Molecular Medicine, University of Padua, Padua 35121, Italy.
Raissa Rilo ChristoffInstitute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-901, Brazil.
Patricia Pestana GarcezInstitute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-901, Brazil.
Ali MirazimiDepartment of Laboratory Medicine (LABMED), Karolinska Institute, Stockholm 17177, Sweden; National Veterinary Institute, Uppsala 75189, Sweden.
Jürgen A KnoblichInstitute of Molecular Biotechnology (IMBA), Austrian Academy of Sciences, Vienna BioCenter (VBC), Vienna 1030, Austria; Medical University of Vienna, Vienna 1030, Austria. Electronic address: juergen.knoblich@imba.oeaw.ac.at.
Austrian Academy of Sciences · ATUniversidade Federal do Rio de Janeiro · BRUniversity of Padua · ITCenter for Experimental and Clinical Infection Research · DEHelmholtz Centre for Infection Research · DEInstitute of Molecular Biotechnology · ATSwedish Veterinary Agency · SE

Funding

Austrian Science Fund FWF F 7803Austrian Science Fund FWF F 7804European Research Council 695642
6 · The paper itself

Abstract

Viral infection in early pregnancy is a major cause of microcephaly. However, how distinct viruses impair human brain development remains poorly understood. Here we use human brain organoids to study the mechanisms underlying microcephaly caused by Zika virus (ZIKV) and herpes simplex virus (HSV-1). We find that both viruses efficiently replicate in brain organoids and attenuate their growth by causing cell death. However, transcriptional profiling reveals that ZIKV and HSV-1 elicit distinct cellular responses and that HSV-1 uniquely impairs neuroepithelial identity. Furthermore, we demonstrate that, although both viruses fail to potently induce the type I interferon system, the organoid defects caused by their infection can be rescued by distinct type I interferons. These phenotypes are not seen in 2D cultures, highlighting the superiority of brain organoids in modeling viral infections. These results uncover virus-specific mechanisms and complex cellular immune defenses associated with virus-induced microcephaly.

Indexed as

Herpesvirus 1, HumanMicrocephalyZika VirusZika Virus InfectionFemaleHumansOrganoidsPregnancybrain organoidsherpes simplex virusinnate immune responseinterferonsmicrocephalyneural progenitorsneuroepithelial polarityZika virus

Identifiers

PMID33838105
PMCPMC7611471
OpenAlexW3146966644

What OpenQuestion holds

Textmetadata
LicenceTDM
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.