Evidence map›Paper›PMID 40461648›Full record

ArticleNature microbiology2025

Herpes simplex virus 1 evades APOBEC1-mediated immunity via its uracil-DNA glycosylase in mice.

Akihisa Kato, Hayato Harima, Yuji Tsunekawa, Manabu Igarashi, Kouichi Kitamura, Kousho Wakae, Tomoaki Nishiyama, Satoru Morimoto, Toru Suzuki, Hiroko Kozuka-Hata and 11 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature microbiology, 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. Review
  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

21 authors.

Akihisa Kato *Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Hayato Harima *Division of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-6704-4601
Yuji TsunekawaDivision of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Manabu IgarashiDivision of Global Epidemiology, International Institute for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Kouichi KitamuraDepartment of Virology II, National Institute of Infectious Diseases Murayama Branch, Musashi-murayama, Japan.ORCID http://orcid.org/0000-0001-9692-8724
Kousho WakaeDepartment of Virology II, National Institute of Infectious Diseases Murayama Branch, Musashi-murayama, Japan.
Tomoaki NishiyamaResearch Center for Experimental Modeling of Human Disease, Kanazawa University, Kanazawa, Japan.
Satoru MorimotoKeio University Regenerative Medicine Research Center, Kanagawa, Japan.
Toru SuzukiDivision of RNA and Gene Regulation, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Hiroko Kozuka-HataMedical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-9286-6594
Masaaki OyamaMedical Proteomics Laboratory, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0001-6478-3735
Daisuke MotookaGenome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Mizuki WatanabeDivision of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Kousuke TakeshimaDivision of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yuhei MaruzuruDivision of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Naoto KoyanagiDivision of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Hideyuki OkanoKeio University Regenerative Medicine Research Center, Kanagawa, Japan.
Toshifumi InadaDivision of RNA and Gene Regulation, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-2695-588X
Takashi OkadaDivision of Molecular and Medical Genetics, Center for Gene and Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Masamichi MuramatsuDepartment of Virology II, National Institute of Infectious Diseases Murayama Branch, Musashi-murayama, Japan.
Yasushi KawaguchiDivision of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. ykawagu@ims.u-tokyo.ac.jp.ORCID http://orcid.org/0000-0001-8232-6925

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Herpes simplex virus 1 (HSV-1) is the most common cause of viral encephalitis, which can be lethal or result in severe neurological defects despite antiviral therapy. The apolipoprotein B messenger-RNA editing enzyme, catalytic polypeptide-like (APOBEC) group of proteins can act as viral restriction factors. How HSV-1 evades this intrinsic immune mechanism is unclear. Here, using human carcinoma HEp-2 cells, we find that phosphorylation and therefore activation of HSV-1 uracil-DNA glycosylase counteracts mouse APOBEC1 DNA-editing activity on HSV-1 genomes. This protects viral genomes, promotes viral replication and encephalitis in the central nervous system of mice. Presence of Apobec1 improved encephalitis outcomes in mice challenged with HSV-1 carrying a mutation in the phosphorylation site of uracil-DNA glycosylase. Treatment with an UNG inhibitor, adeno-associated virus vector expressing UGI, protected wild-type HSV-1-infected mice from lethal encephalitis. These findings identify uracil-DNA glycosylase as a viral factor enabling evasion from intrinsic antiviral immunity mediated by APOBEC1 in the central nervous system and suggests a potential therapeutic approach to treat HSV-1 encephalitis.

Indexed as

APOBEC-1 DeaminaseHerpesvirus 1, HumanImmune EvasionUracil-DNA GlycosidaseAnimalsDisease Models, AnimalEncephalitis, Herpes SimplexFemaleHerpes SimplexHumansMiceMice, Inbred C57BLPhosphorylationVirus ReplicationAPOBEC-1 DeaminaseApobec1 protein, mouseUracil-DNA Glycosidase

Identifiers

PMID40461648

What Socratic holds

Textmetadata
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.