efficiently inhibit HIV-1 transmission from human primary monocyte-derived
dendritic cells to CD4+ T Cells
R. Garg, M.J. Tremblay
Laval University, Medical Biology, Quebec, Canada
Miltefosine (Hexadecylphosphocholine) is a phosphorylcholine ester of
hexadecanol, a membrane-active, alkylphospholipid. Miltefosine is an antiprotozoal
Miltefosine was originally discovered and synthesized as an antineoplastic.
Dendritic cells (DCs) are versatile antigen-presenting cells, play a key
role in HIV-1 infection and dissemination. Indeed, it has been reported that HIV-1 is efficiently transferred from
DCs to CD4+ T cells via different routes (early transfer & late
transfer). In the present study, we investigated the
influence of miltefosine on virus interaction with physiologically relevant
human monocyte-derived dendritic cells.
Methods: Primary human monocyte-derived immature dendritic cells (iDCs) were
first pulsed with NL4-3Balenv (fully competent R5-tropic virus) for 1 hour and
washed. Next iDCs were incubated with or without autologous CD4+ T
cells and either left untreated or treated with different doses of miltefosine.
Viral replication was assayed by measuring the cell-free p24 content at
different time interval. To define whether Miltefosine are
affecting the early and/or late transfer phase, iDCs were first treated with
the antiretroviral drug efavirenz (EFV) before pulsing with virions.
We demonstrate that miltefosine significantly inhibit HIV-1 transmission from iDCs to CD4+
T cells. We provide evidence that miltefosine exert an effect on
both early and late phase transfer event.
these findings represent a new functional role of miltefosine for HIV-1
data set the stage for future development of this class of drug for better
treatment of HIV-1.
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