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Utilization of HIV-1 envelope V3 to identify X4- and R5-specific Tat and LTR sequence signatures

Overview of attention for article published in Retrovirology, May 2016
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Utilization of HIV-1 envelope V3 to identify X4- and R5-specific Tat and LTR sequence signatures
Published in
Retrovirology, May 2016
DOI 10.1186/s12977-016-0266-9
Pubmed ID

Gregory C. Antell, Will Dampier, Benjamas Aiamkitsumrit, Michael R. Nonnemacher, Jeffrey M. Jacobson, Vanessa Pirrone, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W. Williams, Gregory Schwartz, Uri Hershberg, Fred C. Krebs, Brian Wigdahl


HIV-1 entry is a receptor-mediated process directed by the interaction of the viral envelope with the host cell CD4 molecule and one of two co-receptors, CCR5 or CXCR4. The amino acid sequence of the third variable (V3) loop of the HIV-1 envelope is highly predictive of co-receptor utilization preference during entry, and machine learning predictive algorithms have been developed to characterize sequences as CCR5-utilizing (R5) or CXCR4-utilizing (X4). It was hypothesized that while the V3 loop is predominantly responsible for determining co-receptor binding, additional components of the HIV-1 genome may contribute to overall viral tropism and display sequence signatures associated with co-receptor utilization. The accessory protein Tat and the HlV-1 long terminal repeat (LTR) were analyzed with respect to genetic diversity and compared by Jensen-Shannon divergence which resulted in a correlation with both mean genetic diversity as well as the absolute difference in genetic diversity between R5- and X4-genome specific trends. As expected, the V3 domain of the gp120 protein was enriched with statistically divergent positions. Statistically divergent positions were also identified in Tat amino acid sequences within the transactivation and TAR-binding domains, and in nucleotide positions throughout the LTR. We further analyzed LTR sequences for putative transcription factor binding sites using the JASPAR transcription factor binding profile database and found several putative differences in transcription factor binding sites between R5 and X4 HIV-1 genomes, specifically identifying the C/EBP sites I and II, and Sp site III to differ with respect to sequence configuration for R5 and X4 LTRs. These observations support the hypothesis that co-receptor utilization coincides with specific genetic signatures in HIV-1 Tat and the LTR, likely due to differing transcriptional regulatory mechanisms and selective pressures applied within specific cellular targets during the course of productive HIV-1 infection.

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Mendeley readers

The data shown below were compiled from readership statistics for 27 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 27 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 19%
Student > Ph. D. Student 4 15%
Professor > Associate Professor 4 15%
Student > Bachelor 2 7%
Student > Doctoral Student 2 7%
Other 7 26%
Unknown 3 11%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 33%
Immunology and Microbiology 7 26%
Medicine and Dentistry 3 11%
Agricultural and Biological Sciences 2 7%
Mathematics 1 4%
Other 1 4%
Unknown 4 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 06 May 2016.
All research outputs
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Outputs of similar age from Retrovirology
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Altmetric has tracked 14,259,883 research outputs across all sources so far. This one is in the 24th percentile – i.e., 24% of other outputs scored the same or lower than it.
So far Altmetric has tracked 825 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 22nd percentile – i.e., 22% 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 262,404 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them