Methamphetamine increases HIV infectivity in neural progenitor cells

Marta Skowronska, Marisa McDonald, Martina Velichkovska, Ana Rachel Leda, Minseon Park, Michal Toborek

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

HIV-1 infection and methamphetamine (METH) abuse frequently occur simultaneously and may have synergistic pathological effects. Although HIV-positive/active METH users have been shown to have higher HIV viral loads and experience more severe neurological complications than non-users, the direct impact of METH on HIV infection and its link to the development of neurocognitive alternations are still poorly understood. In the present study, we hypothesized that METH impacts HIV infection of neural progenitor cells (NPCs) by a mechanism encompassingNFκB/SP1-mediatedHIVLTRactivation. Mouse and human NPCs were infected with EcoHIV (modified HIV virus infectious to mice) and HIV, respectively, in the presence or absence of METH (50 or 100μM). Pretreatment with METH, but not simultaneous exposure, significantly increased HIV production in both mouse and human NPCs. To determine the mechanisms underlying these effects, cells were transfected with different variants of HIV LTR promoters and then exposed toMETH.METHtreatment induced transcriptional activity of the HIV LTR promotor, an effect that required both NFκB and SP1 signaling. Pretreatment with METH also decreased neuronal differentiation of HIV-infected NPCs in both in vitro and in vivo settings. Importantly, NPC-derived daughter cells appeared to be latently infected with HIV. This study indicates that METH increases HIV infectivity of NPCs, through the NFκB/SP1-dependent activation of theHIVLTRandwith the subsequent alterations of NPC neurogenesis. Such events may underlie METH- exacerbated neurocognitive dysfunction in HIV-infected patients.

Original languageEnglish (US)
Pages (from-to)296-311
Number of pages16
JournalJournal of Biological Chemistry
Volume293
Issue number1
DOIs
StatePublished - Jan 5 2018

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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