Latent or low-level persistent reservoirs of HIV-1 may be the chief hurdle to eradication of infection. In particular, it is thought that latently infected T cells can harbor integrated virus, which cannot be eliminated by current therapeutics. Therefore if therapy is discontinued for any reason, this reservoir rekindles infection. Additional potential reservoirs, such as macrophages or microglia in the brain could serve as long-lived sources of low-level virus production. It is thus imperative to identify and model means to eliminate these reservoirs. This proposal aims to use an in Vivo model, the recently described

Public Health Relevance

Latent or persistent HIV reservoirs are impervious to standard antiretroviral therapy, thus they stand as the chief obstacle to clearence of virus from the body. This project proposes to utilize a novel in vivo humanized mouse model to test strategies based on induction and subsequent targeted elimination of viral reservoirs. If successful, a new type of treatment strategy may be developed based on results obtained.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI096113-03
Application #
8497439
Study Section
Special Emphasis Panel (ZAI1-JBS-A)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
3
Fiscal Year
2013
Total Cost
$349,965
Indirect Cost
$23,254
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Martin, Alyssa R; Pollack, Ross A; Capoferri, Adam et al. (2017) Rapamycin-mediated mTOR inhibition uncouples HIV-1 latency reversal from cytokine-associated toxicity. J Clin Invest 127:651-656
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Gianella, Sara; Taylor, Jeff; Brown, Timothy R et al. (2017) Can research at the end of life be a useful tool to advance HIV cure? AIDS 31:1-4
Bosque, Alberto; Nilson, Kyle A; Macedo, Amanda B et al. (2017) Benzotriazoles Reactivate Latent HIV-1 through Inactivation of STAT5 SUMOylation. Cell Rep 18:1324-1334

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