Journal of Neuroimmune Pharmacology

, Volume 7, Issue 2, pp 306–318

Genetic Knockouts Suggest a Critical Role for HIV Co-Receptors in Models of HIV gp120-Induced Brain Injury

  • Ricky Maung
  • Kathryn E. Medders
  • Natalia E. Sejbuk
  • Maya K. Desai
  • Rossella Russo
  • Marcus Kaul
INVITED REVIEW

Abstract

Infection with HIV-1 frequently affects the brain and causes NeuroAIDS prior to the development of overt AIDS. The HIV-1 envelope protein gp120 interacts with host CD4 and chemokine co-receptors to initiate infection of macrophages and lymphocytes. In addition, the virus or fragments of it, such as gp120, cause macrophages to produce neurotoxins and trigger neuronal injury and apoptosis. Moreover, the two major HIV co-receptors, the chemokine receptors CCR5 and CXCR4, serve numerous physiological functions and are widely expressed beyond immune cells, including cells in the brain. Therefore, HIV co-receptors are poised to play a direct and indirect part in the development of NeuroAIDS. Although rodents are not permissive to infection with wild type HIV-1, viral co-receptors - more than CD4 - are highly conserved between species, suggesting the animals can be suitable models for mechanistic studies addressing effects of receptor-ligand interaction other than infection. Of note, transgenic mice expressing HIV gp120 in the brain share several pathological hallmarks with NeuroAIDS brains. Against this background, we will discuss recently completed or initiated, ongoing studies that utilize HIV co-receptor knockout and viral gp120-transgenic mice as models for in vitro and in vivo experimentation in order to address the potential roles of HIV gp120 and its co-receptors in the development of NeuroAIDS.

Keywords

HIV-1 Infection AIDS NeuroAIDS HAND Chemokine receptor Neurodegeneration Transgenic Knockout Animal model 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Ricky Maung
    • 1
  • Kathryn E. Medders
    • 1
  • Natalia E. Sejbuk
    • 1
  • Maya K. Desai
    • 2
  • Rossella Russo
    • 2
    • 3
  • Marcus Kaul
    • 1
    • 2
    • 4
  1. 1.Infectious and Inflammatory Disease CenterSanford-Burnham Medical Research InstituteLa JollaUSA
  2. 2.Neuroscience, Aging and Stem Cell Research CenterSanford-Burnham Medical Research InstituteLa JollaUSA
  3. 3.Department of PharmacobiologyUniversity of CalabriaArcavacata di RendeItaly
  4. 4.Department of PsychiatryUniversity of CaliforniaLa JollaUSA

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