Evidence map›Paper›PMID 10400782›Full record

ArticleJournal of virology1999

Neural stem cells as engraftable packaging lines can mediate gene delivery to microglia: evidence from studying retroviral env-related neurodegeneration.

W P Lynch, A H Sharpe, E Y Snyder

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.8field-weighted citation impact, top 13% 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

21 citing papers in PubMed, 65 citations in OpenAlex.

  1. Review
  2. Article
  3. Rebound from Inhibition: Self-Correction against Neurodegeneration?Journal of clinical & cellular immunology · 2017
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Identification of a neuronal gene expression signature: role of cell cycle arrest in murine neuronal differentiation in vitro.American journal of physiology. Regulatory, integrative and comparative physiology · 2011
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Viral vectors for gene delivery to the nervous system.Nature reviews. Neuroscience · 2003
    Review
  17. Article
  18. Review
  19. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas.Proceedings of the National Academy of Sciences of the United States of America · 2000
    Article
  20. 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

3 authors at 2 institutions in 1 country.

W P LynchDepartment of Microbiology/Immunology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272, USA.
A H Sharpe
E Y Snyder
Boston Children's Hospital · USBrigham and Women's Hospital · US

Funding

SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI CHEN, CHINFEI · 1985 to 2015
$26.2M
MICROGLIA IN RETROVIRUS INDUCED NEURODEGENERATIONR01NS037614 · NINDS · NORTHEAST OHIO MEDICAL UNIVERSITY · PI LYNCH, WILLIAM P · 2003 to 2007
$1.6M
MICROGLIA IN RETROVIRUS INDUCED NEURODEGENERATIONR29NS037614 · NINDS · NORTHEASTERN OHIO UNIVERSITIES COLL MED · PI LYNCH, WILLIAM P · 1998 to 2002
$299k
PATHOGENESIS OF RETROVIRAL NEUROLOGIC DISEASER01NS031065 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI SHARPE, ARLENE H · 1992 to 1995
–
IMMORTALIZED NEURAL PRECURSORS FOR GENE THERAPY &REPAIRR01NS034247 · NINDS · CHILDREN'S HOSPITAL BOSTON · PI SNYDER, EVAN YALE · 1995 to 1999
–
NICHD NIH HHS P30 HD018655NINDS NIH HHS NS31065NINDS NIH HHS NS34247NINDS NIH HHS NS37614NINDS NIH HHS R01 NS037614NINDS NIH HHS R29 NS037614
6 · The paper itself

Abstract

The induction of spongiform myeloencephalopathy by murine leukemia viruses is mediated primarily by infection of central nervous system (CNS) microglia. In this regard, we have previously shown that CasBrE-induced disease requires late, rather than early, virus replication events in microglial cells (W. P. Lynch et al., J. Virol. 70:8896-8907, 1996). Furthermore, neurodegeneration requires the presence of unique sequences within the viral env gene. Thus, the neurodegeneration-inducing events could result from microglial expression of retroviral envelope protein alone or from the interaction of envelope protein with other viral structural proteins in the virus assembly and maturation process. To distinguish between these possible mechanisms of disease induction, we engineered the engraftable neural stem cell line C17-2 into packaging/producer cells in order to deliver the neurovirulent CasBrE env gene to endogenous CNS cells. This strategy resulted in significant CasBrE env expression within CNS microglia without the appearance of replication competent virus. CasBrE envelope expression within microglia was accompanied by increased expression of activation markers F4/80 and Mac-1 (CD11b) but failed to induce spongiform neurodegenerative changes. These results suggest that envelope expression alone within microglia is not sufficient to induce neurodegeneration. Rather, microglia-mediated disease appears to require neurovirulent Env protein interaction with other viral proteins during assembly or maturation. More broadly, the results presented here prove the efficacy of a novel method by which neural stem cell biology may be harnessed for genetically manipulating the CNS, not only for studying neurodegeneration but also as a paradigm for the disseminated distribution of retroviral vector-transduced genes.

Indexed as

Genes, envGene Transfer TechniquesMicrogliaStem CellsAnimalsCell LineHematopoietic Stem Cell TransplantationMiceNerve DegenerationRetroviridaeRetroviridae Infections

Identifiers

PMID10400782
PMCPMC112769
OpenAlexW2115694589

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.