Humanized Mice as a Tool to Monitor HIV Brain Reservoirs and Effects of Substance Abuse

Project: Research project

Description

 DESCRIPTION: Combination antiretroviral therapy (cART), no matter how effective, cannot eliminate viral infection from its lymphoid and brain reservoirs. The blood-brain-barrier presents a substantive challenge as drug penetrance is often impeded. Moreover, the locale and extent of the viral brain reservoir has yet to be defined. This proposal seeks funds to establish a humanized mouse model to monitor formation of HIV reservoirs in hemato-lymphoid and CNS compartments, and in immune and non-immune cells (such as astrocytes). The focused use of mice carrying human blood and glia in the brain makes applicability to humans problematic. In turn, we are developing a resource that will generate improved animal models to study human glial cells interaction with peripheral immunity during HIV infection. Double humanized mice will be validated as a tool to study effects of substances of abuse on HIV CNS reservoir formation and eradication. Our goals to improve existing humanized mice models are as follows: R21 phase - 1) engraft human astrocytes and confirm their role in CNS HIV reservoir in vivo;and 2) enhance the development and function of human innate immune cells by transgenic expression of human IL-34 and assess cytokine effects on HIV-1 reservoir formation. R33 phase - 1) explore the effects of substances of abuse on formation of CNS reservoir and clearance by new antiretroviral approaches.
StatusFinished
Effective start/end date9/30/157/31/18

Funding

  • National Institutes of Health: $186,246.00
  • National Institutes of Health: $188,125.00

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Substance-Related Disorders
HIV
Brain
Neuroglia
Astrocytes
Penetrance
Human Development
Financial Management
Virus Diseases
Blood-Brain Barrier
Cell Communication
HIV Infections
HIV-1
Immunity
Animal Models
Cytokines
Pharmaceutical Preparations
Therapeutics

ASJC

  • Medicine(all)