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Identification of novel HIV-1 dependency factors in primary CCR4+CCR6+Th17 cells via a genome-wide transcriptional approach

Overview of attention for article published in Retrovirology, December 2015
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Title
Identification of novel HIV-1 dependency factors in primary CCR4+CCR6+Th17 cells via a genome-wide transcriptional approach
Published in
Retrovirology, December 2015
DOI 10.1186/s12977-015-0226-9
Pubmed ID
Authors

Aurélie Cleret-Buhot, Yuwei Zhang, Delphine Planas, Jean-Philippe Goulet, Patricia Monteiro, Annie Gosselin, Vanessa Sue Wacleche, Cécile L. Tremblay, Mohammad-Ali Jenabian, Jean-Pierre Routy, Mohamed El-Far, Nicolas Chomont, Elias K. Haddad, Rafick-Pierre Sekaly, Petronela Ancuta

Abstract

The HIV-1 infection is characterized by profound CD4(+) T cell destruction and a marked Th17 dysfunction at the mucosal level. Viral suppressive antiretroviral therapy restores Th1 but not Th17 cells. Although several key HIV dependency factors (HDF) were identified in the past years via genome-wide siRNA screens in cell lines, molecular determinants of HIV permissiveness in primary Th17 cells remain to be elucidated. In an effort to orient Th17-targeted reconstitution strategies, we investigated molecular mechanisms of HIV permissiveness in Th17 cells. Genome-wide transcriptional profiling in memory CD4(+) T-cell subsets enriched in cells exhibiting Th17 (CCR4(+)CCR6(+)), Th1 (CXCR3(+)CCR6(-)), Th2 (CCR4(+)CCR6(-)), and Th1Th17 (CXCR3(+)CCR6(+)) features revealed remarkable transcriptional differences between Th17 and Th1 subsets. The HIV-DNA integration was superior in Th17 versus Th1 upon exposure to both wild-type and VSV-G-pseudotyped HIV; this indicates that post-entry mechanisms contribute to viral replication in Th17. Transcripts significantly enriched in Th17 versus Th1 were previously associated with the regulation of TCR signaling (ZAP-70, Lck, and CD96) and Th17 polarization (RORγt, ARNTL, PTPN13, and RUNX1). A meta-analysis using the NCBI HIV Interaction Database revealed a set of Th17-specific HIV dependency factors (HDFs): PARG, PAK2, KLF2, ITGB7, PTEN, ATG16L1, Alix/AIP1/PDCD6IP, LGALS3, JAK1, TRIM8, MALT1, FOXO3, ARNTL/BMAL1, ABCB1/MDR1, TNFSF13B/BAFF, and CDKN1B. Functional studies demonstrated an increased ability of Th17 versus Th1 cells to respond to TCR triggering in terms of NF-κB nuclear translocation/DNA-binding activity and proliferation. Finally, RNA interference studies identified MAP3K4 and PTPN13 as two novel Th17-specific HDFs. The transcriptional program of Th17 cells includes molecules regulating HIV replication at multiple post-entry steps that may represent potential targets for novel therapies aimed at protecting Th17 cells from infection and subsequent depletion in HIV-infected subjects.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 68 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Brazil 1 1%
Unknown 67 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 14 21%
Student > Ph. D. Student 12 18%
Student > Bachelor 8 12%
Student > Master 5 7%
Student > Doctoral Student 3 4%
Other 11 16%
Unknown 15 22%
Readers by discipline Count As %
Immunology and Microbiology 12 18%
Biochemistry, Genetics and Molecular Biology 10 15%
Agricultural and Biological Sciences 9 13%
Medicine and Dentistry 8 12%
Computer Science 3 4%
Other 7 10%
Unknown 19 28%
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 15 January 2016.
All research outputs
#13,960,695
of 22,835,198 outputs
Outputs from Retrovirology
#666
of 1,107 outputs
Outputs of similar age
#197,315
of 388,835 outputs
Outputs of similar age from Retrovirology
#14
of 26 outputs
Altmetric has tracked 22,835,198 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,107 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one is in the 37th percentile – i.e., 37% 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 388,835 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 26 others from the same source and published within six weeks on either side of this one. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.