Evidence map›Paper›PMID 37053554›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2023

"Self-inactivating" rabies viruses are susceptible to loss of their intended attenuating modification.

Lei Jin, Makoto Matsuyama, Heather A Sullivan, Mulangma Zhu, Thomas K Lavin, YuanYuan Hou, Nicholas E Lea, Maxwell T Pruner, María Lucía Dam Ferdínez, Ian R Wickersham

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

11 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Rabies virus-based barcoded neuroanatomy resolved by single-cell RNA andbioRxiv : the preprint server for biology · 2023
    Article
  10. Article
  11. 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

10 authors at 1 institution in 1 country.

Lei JinMcGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-7264-4409
Makoto MatsuyamaMcGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0002-7468-2716
Heather A SullivanMcGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Mulangma ZhuMcGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Thomas K LavinMcGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0003-0269-3325
YuanYuan HouMcGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Nicholas E LeaMcGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Maxwell T PrunerMcGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
María Lucía Dam FerdínezMcGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Ian R WickershamMcGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139.ORCID 0000-0003-0389-5324
McGovern Institute for Brain Research · US

Funding

Generation of novel cell type specific mouse genetic toolsU19MH114830 · NIMH · ALLEN INSTITUTE · PI ZENG, HONGKUI · 2017 to 2021
$64.7M
Anatomical characterization of neuronal cell types of the mouse brainU01MH114829 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ASCOLI, GIORGIO A, DONG, HONG-WEI · 2017 to 2021
$13.9M
Re-engineering Rabies VirusRF1MH120017 · NIMH · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WICKERSHAM, IAN R · 2019 to 2019
$2.6M
Novel technologies for nontoxic transsynaptic tracingU01MH106018 · NIMH · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WICKERSHAM, IAN R · 2014 to 2016
$2.5M
NIMH NIH HHS RF1 MH120017NIMH NIH HHS U01 MH106018NIMH NIH HHS U01 MH114829NIMH NIH HHS U19 MH114830
6 · The paper itself

Abstract

Monosynaptic tracing using rabies virus is an important technique in neuroscience, allowing brain-wide labeling of neurons directly presynaptic to a targeted neuronal population. A 2017 article reported the development of a noncytotoxic version-a major advance-based on attenuating the rabies virus by the addition of a destabilization domain to the C terminus of a viral protein. However, this modification did not appear to hinder the ability of the virus to spread between neurons. We analyzed two viruses provided by the authors and show here that both were mutants that had lost the intended modification, explaining the paper's paradoxical results. We then made a virus that actually did have the intended modification in at least the majority of virions and found that it did not spread efficiently under the conditions described in the original paper, namely, without an exogenous protease being expressed in order to remove the destabilization domain. We found that it did spread when the protease was supplied, although this also appeared to result in the deaths of most source cells by 3 wk postinjection. We conclude that the new approach is not robust but that it could become a viable technique given further optimization and validation.

Indexed as

RabiesRabies virusBrainHumansNeuronsPeptide HydrolasesViral ProteinsPeptide HydrolasesViral Proteinsneurosciencerabiesvirus

Identifiers

PMID37053554
PMCPMC9963760
OpenAlexW4319302830

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.