↓ Skip to main content

Tilting the balance between RNA interference and replication eradicates Leishmania RNA virus 1 and mitigates the inflammatory response

Overview of attention for article published in Proceedings of the National Academy of Sciences of the United States of America, October 2016
Altmetric Badge

About this Attention Score

  • Average Attention Score compared to outputs of the same age

Mentioned by

twitter
4 X users

Citations

dimensions_citation
46 Dimensions

Readers on

mendeley
86 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Tilting the balance between RNA interference and replication eradicates Leishmania RNA virus 1 and mitigates the inflammatory response
Published in
Proceedings of the National Academy of Sciences of the United States of America, October 2016
DOI 10.1073/pnas.1615085113
Pubmed ID
Authors

Erin A. Brettmann, Jahangheer S. Shaik, Haroun Zangger, Lon-Fye Lye, F. Matthew Kuhlmann, Natalia S. Akopyants, Dayna M. Oschwald, Katherine L. Owens, Suzanne M. Hickerson, Catherine Ronet, Nicolas Fasel, Stephen M. Beverley

Abstract

Many Leishmania (Viannia) parasites harbor the double-stranded RNA virus Leishmania RNA virus 1 (LRV1), which has been associated with increased disease severity in animal models and humans and with drug treatment failures in humans. Remarkably, LRV1 survives in the presence of an active RNAi pathway, which in many organisms controls RNA viruses. We found significant levels (0.4 to 2.5%) of small RNAs derived from LRV1 in both Leishmania braziliensis and Leishmania guyanensis, mapping across both strands and with properties consistent with Dicer-mediated cleavage of the dsRNA genome. LRV1 lacks cis- or trans-acting RNAi inhibitory activities, suggesting that virus retention must be maintained by a balance between RNAi activity and LRV1 replication. To tilt this balance toward elimination, we targeted LRV1 using long-hairpin/stem-loop constructs similar to those effective against chromosomal genes. LRV1 was completely eliminated, at high efficiency, accompanied by a massive overproduction of LRV1-specific siRNAs, representing as much as 87% of the total. For both L. braziliensis and L. guyanensis, RNAi-derived LRV1-negative lines were no longer able to induce a Toll-like receptor 3-dependent hyperinflammatory cytokine response in infected macrophages. We demonstrate in vitro a role for LRV1 in virulence of L. braziliensis, the Leishmania species responsible for the vast majority of mucocutaneous leishmaniasis cases. These findings establish a targeted method for elimination of LRV1, and potentially of other Leishmania viruses, which will facilitate mechanistic dissection of the role of LRV1-mediated virulence. Moreover, our data establish a third paradigm for RNAi-viral relationships in evolution: one of balance rather than elimination.

X Demographics

X Demographics

The data shown below were collected from the profiles of 4 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 86 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 86 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 12 14%
Researcher 12 14%
Student > Master 11 13%
Student > Bachelor 9 10%
Professor 6 7%
Other 13 15%
Unknown 23 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 30 35%
Agricultural and Biological Sciences 11 13%
Immunology and Microbiology 5 6%
Medicine and Dentistry 4 5%
Veterinary Science and Veterinary Medicine 2 2%
Other 8 9%
Unknown 26 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 31 January 2018.
All research outputs
#15,537,011
of 24,625,114 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#89,545
of 101,438 outputs
Outputs of similar age
#186,222
of 322,432 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#819
of 1,001 outputs
Altmetric has tracked 24,625,114 research outputs across all sources so far. This one is in the 34th percentile – i.e., 34% of other outputs scored the same or lower than it.
So far Altmetric has tracked 101,438 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 38.8. This one is in the 10th percentile – i.e., 10% of its peers scored the same or lower than it.
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 322,432 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1,001 others from the same source and published within six weeks on either side of this one. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.