The antiviral compound BIT225 inhibits HIV-1 replication in myeloid dendritic cells. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Khoury, Gabriela; Ewart, Gary; Luscombe, Carolyn; Miller, Michelle; Wilkinson, John
• Is Part Of: AIDS research and therapy. Volume 13:Issue 1(2016)
• Page Start: 1
• Page End: 5
• Publication Date: 2016-12
• Subjects: HIV-1 -- Antiviral -- Myeloid -- Dendritic cells -- Viral transfer; AIDS (Disease) -- Periodicals; 616.9792005
• DOI: 10.1186/s12981-016-0093-z
• Languages: English
• ISSNs: 1742-6405

Abstract

Abstract Background 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). 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.