title: The antiviral compound BIT225 inhibits HIV-1 replication in myeloid dendritic cells.
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.
authors: Biotron Limited, Suite 1.9, 56 Delhi Road, North Ryde, Sydney, NSW 2013 Australia.
authors: Gabriela
authors: G
authors: Khoury
authors: Biotron Limited, Suite 1.9, 56 Delhi Road, North Ryde, Sydney, NSW 2013 Australia.
authors: Gary
authors: G
authors: Ewart
authors: Biotron Limited, Suite 1.9, 56 Delhi Road, North Ryde, Sydney, NSW 2013 Australia.
authors: Carolyn
authors: C
authors: Luscombe
authors: Biotron Limited, Suite 1.9, 56 Delhi Road, North Ryde, Sydney, NSW 2013 Australia.
authors: Michelle
authors: M
authors: Miller
authors: Biotron Limited, Suite 1.9, 56 Delhi Road, North Ryde, Sydney, NSW 2013 Australia.
authors: John
authors: J
authors: Wilkinson
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D003713:Dendritic Cells / Q000821:virology*; D006146:Guanidines / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D022423:Myeloid Cells / Q000821:virology*; D011720:Pyrazoles / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D006146:Guanidines; C570889:N-(5-(1-methyl-1H-pyrazol-4-yl)-napthalene-2-carbonyl)guanidine; D011720:Pyrazoles
keywords: Antiviral; Dendritic cells; HIV-1; Myeloid; Viral transfer