Browsing by Author "Berman, Joan"

Now showing 1 - 1 of 1
  • No Thumbnail Available
    Item
    HIV infection of astrocytes increases release of Dickkopf-1 protein by a gap junction and hemichannel dependent mechanism
    (Springer, 2012) Orellana Roca, Juan Andrés; Sáez, Juan Carlos; Berman, Joan; Eugenín Arce, Eliseo Alberto
    Human immunodeficiency virus-1 (HIV) is a major public health issue, with a significant CNS complication of infection, NeuroAIDS. In vivo, microglia/macrophages are the main cells infected. However, a low but significant number of HIV infected astrocytes also has been detected, but their role in the pathogenesis of NeuroAIDS is not well understood. Our previous data indicated that HIV infection of astrocytes increased expression of the glycoprotein, dickkopf-1 protein (Dkk1), a soluble inhibitor of the wnt pathway. In HIV infected cultures of human astrocytes, secretion of Dkk1 was highly regulated by functional gap junction channels and connexin43 hemichannels. We also demonstrated that Dkk1 expression in astrocytes was increased in human brain tissue sections of individuals with HIV encephalitis as compared to tissue sections from uninfected individuals. We demonstrated that in primary cells, Dkk1 secretion did not participate in bystander killing of uninfected astrocytes or viral reactivation. However, its secretion regulates neuronal damage measured by collapse of neuronal processes. Thus, we demonstrated that HIV infection of astrocytes dysregulates secretion of Dkk1 by a mechanisms that involves both gap junctions as well as hemichannels that contributes to the neuropathogenesis observed in HIV infected individuals.