Evidence map›Paper›PMID 30201994›Full record

ArticleNature immunology2018

Combating herpesvirus encephalitis by potentiating a TLR3-mTORC2 axis.

Ryota Sato, Akihisa Kato, Takahiko Chimura, Shin-Ichiroh Saitoh, Takuma Shibata, Yusuke Murakami, Ryutaro Fukui, Kaiwen Liu, Yun Zhang, Jun Arii and 7 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
6.5field-weighted citation impact, top 3% 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

46 citing papers in PubMed, 68 citations in OpenAlex.

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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

17 authors at 5 institutions in 2 countries.

Ryota SatoDivision of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Akihisa KatoDivision of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Takahiko ChimuraDivision of Neuronal Network, Department of Basic Medical Sciences, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Shin-Ichiroh SaitohDivision of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Takuma ShibataDivision of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yusuke MurakamiDivision of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Ryutaro FukuiDivision of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Kaiwen LiuDivision of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yun ZhangDivision of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Jun AriiDivision of Molecular Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Ge-Hong Sun-WadaDepartment of Biochemistry, Faculty of Pharmaceutical Sciences, Doshisha Women's College, Kyoto, Japan.
Yoh WadaDivision of Biological Science, Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
Tsuneo IkenoueDivision of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Glen N BarberUM/Sylvester Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
Toshiya ManabeDivision of Neuronal Network, Department of Basic Medical Sciences, The Institute of Medical Science, The University of Tokyo, Tokyo, 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.
Kensuke MiyakeDivision of Innate Immunity, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. kmiyake@ims.u-tokyo.ac.jp.ORCID http://orcid.org/0000-0001-6629-226X
The University of Tokyo · JPNational Institute of Infectious Diseases · JPDoshisha Women's College of Liberal Arts · JPOsaka Research Institute of Industrial Science and Technology · JPUniversity of Miami · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TLR3 is a sensor of double-stranded RNA that is indispensable for defense against infection with herpes simplex virus type 1 (HSV-1) in the brain. We found here that TLR3 was required for innate immune responses to HSV-1 in neurons and astrocytes. During infection with HSV-1, TLR3 recruited the metabolic checkpoint kinase complex mTORC2, which led to the induction of chemokines and trafficking of TLR3 to the cell periphery. Such trafficking enabled the activation of molecules (including mTORC1) required for the induction of type I interferons. Intracranial infection of mice with HSV-1 was exacerbated by impairment of TLR3 responses with an inhibitor of mTOR and was significantly 'rescued' by potentiation of TLR3 responses with an agonistic antibody to TLR3. These results suggest that the TLR3-mTORC2 axis might be a therapeutic target through which to combat herpes simplex encephalitis.

Indexed as

AnimalsEncephalitis, Herpes SimplexHerpesvirus 1, HumanImmunity, InnateMechanistic Target of Rapamycin Complex 2MiceMice, Inbred BALB CMice, Inbred C57BLNIH 3T3 CellsToll-Like Receptor 3Mechanistic Target of Rapamycin Complex 2TLR3 protein, mouseToll-Like Receptor 3

Identifiers

PMID30201994
OpenAlexW2889979805

What OpenQuestion 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 OpenQuestion graph.