Evidence map›Paper›PMID 39505878›Full record

ArticleNPJ vaccines2024

CRISPR/Cas9 screens identify key host factors that enhance rotavirus reverse genetics efficacy and vaccine production.

Yinxing Zhu, Meagan E Sullender, Danielle E Campbell, Leran Wang, Sanghyun Lee, Takahiro Kawagishi, Gaopeng Hou, Alen Dizdarevic, Philippe H Jais, Megan T Baldridge and 1 more

Abstract read
In one paragraph

Article in NPJ vaccines, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–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

8 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Fatty acid 2-hydroxylase facilitates rotavirus uncoating and endosomal escape.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. 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

11 authors.

Yinxing ZhuDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Meagan E SullenderDepartment of Medicine, Division of Infectious Diseases and Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
Danielle E CampbellDepartment of Medicine, Division of Infectious Diseases and Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
Leran WangDepartment of Medicine, Division of Infectious Diseases and Edison Family Center for Genome Sciences & Systems Biology, Washington University School of Medicine, St. Louis, MO, USA.
Sanghyun LeeDivision of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.ORCID http://orcid.org/0000-0002-0736-1648
Takahiro KawagishiDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Gaopeng HouDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Alen DizdarevicDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
Philippe H JaisEukarÿs SAS, Pépinière Genopole, 4 rue Pierre Fontaine, Genopole Entreprises Campus 3, 4 Rue Pierre Fontaine 91000, Evry-Courcouronnes, France.
Megan T BaldridgeDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. mbaldridge@wustl.edu.ORCID http://orcid.org/0000-0002-7030-6131
Siyuan DingDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA. siyuan.ding@wustl.edu.ORCID http://orcid.org/0000-0002-5338-260X

Funding

The role of Sirtuins in neurodegenerative diseaseP20GM109035 · NIGMS · BROWN UNIVERSITY · PI WONG, IAN Y · 2016 to 2025
$22.6M
Enterovirus interference with rotavirus vaccine replication and immunityR01AI173360 · NIAID · WASHINGTON UNIVERSITY · PI Megan T Baldridge, Vanessa Catherine HARRIS · 2023 to 2026
$2.9M
Interferon-Stimulated Gene Inhibition of Rotavirus Replication and Viral AntagonismR01AI150796 · NIAID · WASHINGTON UNIVERSITY · PI DING, SIYUAN · 2020 to 2024
$2.0M
Viral immune evasion during intestinal norovirus infectionR01AI183155 · NIAID · BROWN UNIVERSITY · PI Sanghyun Lee · 2024 to 2026
$1.7M
Entry inhibition of SARS-CoV-2 by human LRRC15R21AI173821 · NIAID · BROWN UNIVERSITY · PI LEE, SANGHYUN · 2023 to 2024
$460k
Mechanism of Rotavirus EntryR21AI168490 · NIAID · WASHINGTON UNIVERSITY · PI DING, SIYUAN · 2023 to 2024
$428k
NIAID NIH HHS R01 AI150796NIAID NIH HHS R01 AI173360NIAID NIH HHS R01 AI183155NIAID NIH HHS R21 AI168490NIAID NIH HHS R21 AI173821NIGMS NIH HHS P20 GM109035
6 · The paper itself

Abstract

Rotaviruses pose a significant threat to young children. To identify novel pro- and anti-rotavirus host factors, we performed genome-wide CRISPR/Cas9 screens using rhesus rotavirus and African green monkey cells. Genetic deletion of either SERPINB1 or TMEM236, the top two antiviral factors, in MA104 cells increased virus titers in a rotavirus strain independent manner. Using this information, we optimized the existing rotavirus reverse genetics systems by combining SERPINB1 knockout MA104 cells with a C3P3-G3 helper plasmid. We improved the recovery efficiency and rescued several low-titer rotavirus reporter and mutant strains that prove difficult to rescue otherwise. Furthermore, we demonstrate that TMEM236 knockout in Vero cells supported higher yields of two live-attenuated rotavirus vaccine strains than the parental cell line and represents a more robust vaccine-producing cell substrate. Collectively, we developed a third-generation optimized rotavirus reverse genetics system and generated gene-edited Vero cells as a new substrate for improving rotavirus vaccine production.

Identifiers

PMID39505878
PMCPMC11542071

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.