Miltefosine represses HIV-1 replication in human dendritic cell/T-cell cocultures partially by inducing secretion of type-I interferon.
Miltefosine (Milt) was originally synthesized as an antineoplastic agent but this phospholipid drug is now clinically used as an antiprotozoal compound. We demonstrate here that Milt reduces replication of HIV-1 in cocultures of human dendritic cells (DCs) and CD4(+) T cells. This phenomenon is due to a rapid secretion of soluble factors by DCs. We present evidence that the Milt-mediated repression in virus production is associated with induction of type-I interferon (IFN) in DCs. The Milt-dependent diminution in HIV-1 production was not totally abrogated by B18R, a vaccinia virus-encoded neutralizing type-I IFN receptor, which suggests the involvement of another yet to be identified soluble factor. Altogether, these results suggest that a therapy with Milt when used to control protozoan infections in individuals also carrying HIV-1 might also help to limit viral load. Additional studies are warranted to estimate the exact therapeutic potential of Milt as an anti-HIV-1 agent.
Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec, CHUL, Canada.
Ravendra
R
Garg
Michel J
MJ
Tremblay
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D007370:Interferon Type I; D010767:Phosphorylcholine; C039128:miltefosine