The antiviral compound BIT225 inhibits HIV-1 replication in myeloid dendritic cells
- **riela Khoury,
- Gary Ewart,
- Carolyn Luscombe,
- Michelle Miller and
- John WilkinsonEmail author
AIDS Research and Therapy2016
13:7
https://doi.org/10.1186/s12981-016-0093-z
© Khoury et al. 2016
- Received: 2 December 2015
- Accepted: 26 January 2016
- Published: 8 February 2016
Abstract
Background
Previous studies with BIT225 (
N-carbamimidoyl-5-(1-methyl-1
H-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).
Results
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.
Conclusions
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.
https://aidsrestherapy.biomedcentral.com/articles/10.1186/s12981-016-0093-z
This was in-vitro only, but still, shows action against dendritic cells.
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