Miltefosine represses HIV-1 replication in human dendritic cell/T-cell cocultures partially by inducing secretion of type-I interferon

Virology. 2012 Oct 25;432(2):271-6. doi: 10.1016/j.virol.2012.05.032. Epub 2012 Jun 15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology*
  • Cell Line
  • Coculture Techniques
  • Dendritic Cells / immunology*
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Interferon Type I / metabolism*
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / pharmacology
  • Virus Replication / drug effects*

Substances

  • Interferon Type I
  • Phosphorylcholine
  • miltefosine