Details

Autor(en) / Beteiligte

• Rom, Inna
• Deshmane, Satish L
• Mukerjee, Ruma
• Khalili, Kamel
• Amini, Shohreh
• Sawaya, Bassel E

Titel

HIV-1 Vpr deregulates calcium secretion in neural cells

Ist Teil von

• Brain research, 2009-06, Vol.1275, p.81-86

Ort / Verlag

Amsterdam: Elsevier B.V

Erscheinungsjahr

2009

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract The lack of productive infection of neurons by HIV-1 suggests that the neuronal damage seen in AIDS patients with cognitive disorders is caused indirectly via viral and cellular proteins with neurotoxic activity. Among HIV-1 proteins, Vpr has been shown to deregulate expression of various important cytokines and inflammatory proteins in infected and uninfected cells. However, the mechanisms underlying these changes remain unclear. Here, we demonstrate that neurons can take up Vpr that is released into the supernatant of HIV-infected microglia. We also found that administration of recombinant Vpr (rVpr) to human neurons resulted in a slow but sustained elevation of intracellular calcium [Ca2+ ]i. Interestingly, our data also show that [Ca2+ ]i elevation by Vpr leads to ROS production and impairs glutamate signaling in neuronal cells. Vpr disturbs calcium homeostasis through downregulation of endogenous PMCA. Finally, we found that the permeability of the plasma membrane increases in neurons treated with Vpr. Therefore, we conclude that soluble Vpr is a major viral factor that causes a disturbance in neuronal communication leading to neuronal dysfunction. The outcome of these studies will advance the understanding of HIV-1 pathogenesis and will help in the development of new therapeutic approaches.