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The antiviral compound BIT225 inhibits HIV-1 replication in myeloid dendritic cells

Overview of attention for article published in AIDS Research and Therapy, February 2016
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Title
The antiviral compound BIT225 inhibits HIV-1 replication in myeloid dendritic cells
Published in
AIDS Research and Therapy, February 2016
DOI 10.1186/s12981-016-0093-z
Pubmed ID
Authors

Gabriela Khoury, Gary Ewart, Carolyn Luscombe, Michelle Miller, John Wilkinson

Abstract

Previous studies with BIT225 (N-carbamimidoyl-5-(1-methyl-1H-pyrazol-4-yl)-2-naphthamide) have demonstrated a unique antiviral activity that blocks the release of HIV-1 from monocyte-derived macrophages (MDM). Antagonising the ion channel formed by HIV-1 Vpu, BIT225 preferentially targets de novo intracellular virus produced in 'virus-containing compartments' of MDM. In primary infections, dendritic cells (DC) are one of the first cells infected by HIV-1 and can transfer virus to more permissive CD4(+) T cells, making these cells an important target for novel antiviral therapies. To extend previous findings with BIT225, we aimed to further characterise the antiviral activity of BIT225 on HIV-1 replication in monocyte-derived DC (MDDC). The anti-HIV-1 activity of BIT225 was evaluated in vitro within MDDC alone and in co-cultures with activated CD4(+) T cells to examine the effect of the drug on HIV-1 transfer. Antiviral activity was determined by measuring HIV-1 reverse transcriptase activity in the culture supernatant of BIT225 treated and DMSO control cultures. A single dose of BIT225 resulted in a mean (SE) peak inhibition of HIV-1 release from MDDC by 74.5 % (±0.6) following 14 days of culture and a 6-fold reduction of HIV-1 transfer to activated uninfected CD4(+) T cells in co-culture. HIV-1 release from MDDC was inhibited by BIT225. This data broadens the drug's antiviral activity profile within cells of the myeloid lineage. These findings suggest a potential role for BIT225 in reducing HIV-1 production and preventing viral dissemination in early and chronic infection and may assist in limiting virus spread with any ongoing viral replication during antiretroviral therapy.

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The data shown below were collected from the profiles of 2 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 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 3 27%
Student > Master 2 18%
Researcher 2 18%
Student > Bachelor 1 9%
Unknown 3 27%
Readers by discipline Count As %
Medicine and Dentistry 2 18%
Immunology and Microbiology 1 9%
Agricultural and Biological Sciences 1 9%
Neuroscience 1 9%
Chemistry 1 9%
Other 0 0%
Unknown 5 45%
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 10 February 2016.
All research outputs
#15,161,227
of 23,317,888 outputs
Outputs from AIDS Research and Therapy
#331
of 574 outputs
Outputs of similar age
#225,743
of 401,335 outputs
Outputs of similar age from AIDS Research and Therapy
#13
of 23 outputs
Altmetric has tracked 23,317,888 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 574 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.6. This one is in the 38th percentile – i.e., 38% 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 401,335 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 23 others from the same source and published within six weeks on either side of this one. This one is in the 39th percentile – i.e., 39% of its contemporaries scored the same or lower than it.