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Potent and reversible lentiviral vector restriction in murine induced pluripotent stem cells

Overview of attention for article published in Retrovirology, May 2017
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (77th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (57th percentile)

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1 blog
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3 X users

Citations

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10 Dimensions

Readers on

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38 Mendeley
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2 CiteULike
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Title
Potent and reversible lentiviral vector restriction in murine induced pluripotent stem cells
Published in
Retrovirology, May 2017
DOI 10.1186/s12977-017-0358-1
Pubmed ID
Authors

Franziska K. Geis, Melanie Galla, Dirk Hoffmann, Johannes Kuehle, Daniela Zychlinski, Tobias Maetzig, Juliane W. Schott, Adrian Schwarzer, Christine Goffinet, Stephen P. Goff, Axel Schambach

Abstract

Retroviral vectors are derived from wild-type retroviruses, can be used to study retrovirus-host interactions and are effective tools in gene and cell therapy. However, numerous cell types are resistant or less permissive to retrovirus infection due to the presence of active defense mechanisms, or the absence of important cellular host co-factors. In contrast to multipotent stem cells, pluripotent stem cells (PSC) have potential to differentiate into all three germ layers. Much remains to be elucidated in the field of anti-viral immunity in stem cells, especially in PSC. In this study, we report that transduction with HIV-1-based, lentiviral vectors (LV) is impaired in murine PSC. Analyses of early retroviral events in induced pluripotent stem cells (iPSC) revealed that the restriction is independent of envelope choice and does not affect reverse transcription, but perturbs nuclear entry and proviral integration. Proteasomal inhibition by MG132 could not circumvent the restriction. However, prevention of cyclophilin A (CypA) binding to the HIV-1 capsid via use of either a CypA inhibitor (cyclosporine A) or CypA-independent capsid mutants improved transduction. In addition, application of higher vector doses also increased transduction. Our data revealed a CypA mediated restriction in iPSC, which was acquired during reprogramming, associated with pluripotency and relieved upon subsequent differentiation. We showed that murine PSC and iPSC are less susceptible to LV. The block observed in iPSC was CypA-dependent and resulted in reduced nuclear entry of viral DNA and proviral integration. Our study helps to improve transduction of murine pluripotent cells with HIV-1-based vectors and contributes to our understanding of retrovirus-host interactions in PSC.

X Demographics

X Demographics

The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 38 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 21%
Researcher 7 18%
Professor 3 8%
Student > Master 3 8%
Student > Bachelor 2 5%
Other 7 18%
Unknown 8 21%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 24%
Immunology and Microbiology 7 18%
Agricultural and Biological Sciences 6 16%
Medicine and Dentistry 2 5%
Nursing and Health Professions 1 3%
Other 2 5%
Unknown 11 29%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 8. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 February 2018.
All research outputs
#3,819,964
of 22,977,819 outputs
Outputs from Retrovirology
#183
of 1,109 outputs
Outputs of similar age
#68,757
of 316,427 outputs
Outputs of similar age from Retrovirology
#6
of 14 outputs
Altmetric has tracked 22,977,819 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,109 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has done well, scoring higher than 83% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 316,427 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 77% of its contemporaries.
We're also able to compare this research output to 14 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 57% of its contemporaries.