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Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model

Overview of attention for article published in Retrovirology, December 2014
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Title
Diminished transmission of drug resistant HIV-1 variants with reduced replication capacity in a human transmission model
Published in
Retrovirology, December 2014
DOI 10.1186/s12977-014-0113-9
Pubmed ID
Authors

Marieke Pingen, Ramin Sarrami-Forooshani, Annemarie MJ Wensing, Petra van Ham, Agata Drewniak, Charles AB Boucher, Teunis BH Geijtenbeek, Monique Nijhuis

Abstract

BackgroundDifferent patterns of drug resistance are observed in treated and therapy naïve HIV-1 infected populations. Especially the NRTI-related M184I/V variants, which are among the most frequently encountered mutations in treated patients, are underrepresented in the antiretroviral naïve population. M184I/V mutations are known to have a profound effect on viral replication and tend to revert over time in the new host. However it is debated whether a diminished transmission efficacy of HIV variants with a reduced replication capacity can also contribute to the observed discrepancy in genotypic patterns.As dendritic cells (DCs) play a pivotal role in HIV-1 transmission, we used a model containing primary human Langerhans cells (LCs) and DCs to compare the transmission efficacy M184 variants (HIV-M184V/I/T) to HIV wild type (HIV-WT). As control, we used HIV harboring the NNRTI mutation K103N (HIV-K103N) which has a minor effect on replication and is found at a similar prevalence in treated and untreated individuals.ResultsIn comparison to HIV-WT, the HIV-M184 variants were less efficiently transmitted to CCR5+ Jurkat T cells by both LCs and DCs. The transmission rate of HIV-K103N was slightly reduced to HIV-WT in LCs and even higher than HIV-WT in DCs. Replication experiments in CCR5+ Jurkat T cells revealed no apparent differences in replication capacity between the mutant viruses and HIV-WT. However, viral replication in LCs and DCs was in concordance with the transmission results; replication by the HIV-M184 variants was lower than replication by HIV-WT, and the level of replication of HIV-K103N was intermediate for LCs and higher than HIV-WT for DCs.ConclusionsOur data demonstrate that drug resistant M184-variants display a reduced replication capacity in LCs and DCs which directly impairs their transmission efficacy. As such, diminished transmission efficacy may contribute to the lower prevalence of drug resistant variants in therapy naive individuals.

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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 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 4%
Argentina 1 4%
Unknown 26 93%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 21%
Researcher 5 18%
Professor 4 14%
Student > Doctoral Student 3 11%
Student > Master 3 11%
Other 2 7%
Unknown 5 18%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 29%
Immunology and Microbiology 7 25%
Medicine and Dentistry 5 18%
Mathematics 1 4%
Biochemistry, Genetics and Molecular Biology 1 4%
Other 1 4%
Unknown 5 18%
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 14 October 2015.
All research outputs
#13,418,835
of 22,775,504 outputs
Outputs from Retrovirology
#624
of 1,106 outputs
Outputs of similar age
#174,171
of 354,996 outputs
Outputs of similar age from Retrovirology
#10
of 19 outputs
Altmetric has tracked 22,775,504 research outputs across all sources so far. This one is in the 39th percentile – i.e., 39% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,106 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one is in the 41st percentile – i.e., 41% 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 354,996 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 49th percentile – i.e., 49% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 19 others from the same source and published within six weeks on either side of this one. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.