Latently infected, quiescent CD4 T cells represent a central obstacle to eradication of HIV-1. Major hurdles are the low frequencies of latently infected cells in peripheral blood and the lack of known phenotypic markers that can distinguish them from uninfected ones. These impediments have prompted the development of in vitro cell models of latency, which. Such models allow manipulation of cellular and viral characteristics to gain a mechanistic understanding of how latency is established and regulated. However, no single experimental system of HIV latency is perceived to completely recapitulate the biology ofthe latent viral reservoir in vivo. This is mainly because (a) the mechanisms for establishment of latency by HIV are multiple;and (b) the types of cells harboring latent reservoirs are also multiple. A wealth of knowledge has been gained regarding how specific stimuli (e.g. activation/differentiation, homeostatic proliferation, cytokines) and viral factors (e.g. integration site, Tat-driven expression) influence the dynamics of latent reservoirs in experimental systems. Project 2.2 will perform

Public Health Relevance

Within the Deianey Collaboratory program, the overall goal of Project 2.2 is the application of in vitro primary cell culture systems to identify new drug-like substances and combinations that will activate latent HIV in biological systems, prior to studies in animals and humans. A second aspect of these studies is to begin to identify the mechanims of action of such drugs, such that future studies can focus on identification of novel cellular targets and pathways, which will broaden of the scope of therapeutic possibilities in the near future.

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 #
8497430
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
$300,023
Indirect Cost
$23,255
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Davis, Zachary B; Cogswell, Andrew; Scott, Hamish et al. (2016) A Conserved HIV-1-Derived Peptide Presented by HLA-E Renders Infected T-cells Highly Susceptible to Attack by NKG2A/CD94-Bearing Natural Killer Cells. PLoS Pathog 12:e1005421
Imaz, Arkaitz; Martinez-Picado, Javier; Niubó, Jordi et al. (2016) HIV-1-RNA Decay and Dolutegravir Concentrations in Semen of Patients Starting a First Antiretroviral Regimen. J Infect Dis 214:1512-1519
Honeycutt, Jenna B; Wahl, Angela; Baker, Caroline et al. (2016) Macrophages sustain HIV replication in vivo independently of T cells. J Clin Invest 126:1353-66
Tokarev, Andrey; Stoneham, Charlotte; Lewinski, Mary K et al. (2016) Pharmacologic Inhibition of Nedd8 Activation Enzyme Exposes CD4-Induced Epitopes within Env on Cells Expressing HIV-1. J Virol 90:2486-502
Victor Garcia, J (2016) Humanized mice for HIV and AIDS research. Curr Opin Virol 19:56-64
Smith, Davey M; Nakazawa, Masato; Freeman, Michael L et al. (2016) Asymptomatic CMV Replication During Early Human Immunodeficiency Virus (HIV) Infection Is Associated With Lower CD4/CD8 Ratio During HIV Treatment. Clin Infect Dis 63:1517-1524
Gianella, Sara; Anderson, Christy M; Var, Susanna R et al. (2016) Replication of Human Herpesviruses Is Associated with Higher HIV DNA Levels during Antiretroviral Therapy Started at Early Phases of HIV Infection. J Virol 90:3944-52
Garcia, J Victor (2016) In vivo platforms for analysis of HIV persistence and eradication. J Clin Invest 126:424-31
Lee, Sook-Kyung; Zhou, Shuntai; Baldoni, Pedro L et al. (2016) Quantification of the Latent HIV-1 Reservoir Using Ultra Deep Sequencing and Primer ID In A Viral Outgrowth Assay. J Acquir Immune Defic Syndr :
Wagner, Gabriel A; Chaillon, Antoine; Liu, Siqi et al. (2016) HIV-associated neurocognitive disorder is associated with HIV-1 dual infection. AIDS 30:2591-2597

Showing the most recent 10 out of 187 publications