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Journal of Neuroimmune Pharmacology

, Volume 7, Issue 2, pp 319–331 | Cite as

Delineating HIV-Associated Neurocognitive Disorders Using Transgenic Models: The Neuropathogenic Actions of Vpr

  • Christopher PowerEmail author
  • Elizabeth Hui
  • Pornpun Vivithanaporn
  • Shaona Acharjee
  • Maria Polyak
INVITED REVIEW

Abstract

HIV-associated neurocognitive disorders (HAND) represent a constellation of neurological disabilities defined by neuropsychological impairments, neurobehavioral abnormalities and motor deficits. To gain insights into the mechanisms underlying the development of these disabilities, several transgenic models have been developed over the past two decades, which have provided important information regarding the cellular and molecular factors contributing to the neuropathogenesis of HAND. Herein, we concentrate on the neuropathogenic effects of HIV-1 Vpr expressed under the control of c-fms, resulting transgene expression in myeloid cells in both the central and peripheral nervous systems. Vpr’s actions, possibly through its impact on cell cycle machinery, in brain culminate in neuronal and astrocyte injury and death through apoptosis involving activation of caspases-3, -6 and −9 depending on the individual target cell type. Indeed, these outcomes are also induced by soluble Vpr implying Vpr’s effects stem from direct interaction with target cells. Remarkably, in vivo transgenic Vpr expression induces a neurodegenerative phenotype defined by neurobehavioral deficits and neuronal loss in the absence of frank inflammation. Implantation of another viral protein, hepatitis C virus (HCV) core, into Vpr transgenic animals’ brains stimulated neuroinflammation and amplified the neurodegenerative disease phenotype, thereby recapitulating HCV’s putative neuropathogenic actions. The availability of different transgenic models to study HIV neuropathogenesis represents exciting and innovative approaches to understanding disease mechanisms and perhaps developing new therapeutic strategies in the future.

Keywords

HIV-1 Neuropathogenesis Transgenic mouse Vpr Dementia 

Notes

Acknowledgements

EH and PV are supported by fellowships from Alberta Innovates-Health Solutions (AI-HS). CP is supported by a Canada Research Chair in Neurological Infection and Immunity and is an AI-HS Senior Scholar.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Christopher Power
    • 1
    • 3
    Email author
  • Elizabeth Hui
    • 1
  • Pornpun Vivithanaporn
    • 1
    • 2
  • Shaona Acharjee
    • 1
  • Maria Polyak
    • 1
  1. 1.Department of Medicine (Neurology)University of Alberta, Heritage Medical Research CenterEdmontonCanada
  2. 2.Department of Pharmacology, Faculty of ScienceMahidol UniversityBangkokThailand
  3. 3.Division of Neurology6–11 Heritage Medical Research Centre, University of AlbertaEdmontonCanada

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