UnipolarA paper by Marta Skowronska “Methamphetamine increases HIV infectivity in neural progenitor cells” was accepted in the Journal of Biological Chemistry. The co-authors are Marisa McDonald, Martina Velichkovska, Ana Rachel Leda, Minseon Park, and Michal Toborek.

Congratulations to Marta and co-authors!

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 (NPC) by a mechanism encompassing NFκB/SP1-mediated HIV-LTR activation. Mouse and human NPC were infected with EcoHIV (modified HIV virus infectious to mice) and HIV, respectively, in the presence or absence of METH (50 or 100 µM). Pretreatment with METH, but not simultaneous exposure, significantly increased HIV production in both mouse and human NPC. To determine the mechanisms underlying these effects, cells were transfected with different variants of HIV-LTR promoters and then exposed to METH. METH treatment induced transcriptional activity of HIV-LTR promotor, an effect that required both NFκB and SP1 signaling. Pretreatment with METH also decreased neuronal differentiation of HIV-infected NPC 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 NPC, through the NFκB/SP1-dependent activation of HIV LTR, and with the subsequent alterations of NPC neurogenesis. Such events may underlie METH- exacerbated neurocognitive dysfunction in HIV-infected patients.

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